We'll see Peyton Manning sport his new colors against Tom Brady and the New England Patriots. The defending Super Bowl champions have a bevy of marquee matchups including the Pittsburgh Steelers and Green Bay Packers.
And of course, who could forget the top two rookie quarterbacks in Andrew Luck and Robert Griffin III starting their NFL careers?
Here is a look at the 20 biggest games of the 2012 NFL season.
It's the opening game of the 2012 NFL season and it pits bitter rivals against each other.
Need I say more?
Final Score: Giants 30, Cowboys 24
While this game may not be exciting as last year's Green Bay Packers-New Orleans Saints opening game, it will still be a fantastic game.
Look for the defending Super Bowl champions to begin defense of the title with a big divisional win.
Peyton Manning missed the entire 2011 season, and Sunday night on September 9th is the first time that the NFL will see Manning in a regular season game not wearing blue and white on his jersey.
I'm sure Manning was hoping for an easy first game with the Denver Broncos, but instead, he'll get an extremely aggressive defense as the Pittsburgh Steelers travel to Denver. When you factor in that Pittsburgh will be looking to repay the Broncos for knocking them out of the playoffs last year, this matchup becomes even more difficult for Manning.
It will be interesting to see what type of relationship that Manning has with his receivers in this first game. Considering how much pressure the Steelers are able to get on quarterbacks, if Manning and his receivers are on a different page, this could be a long game for the Broncos.
Final Score: Steelers 27, Broncos 21
The 2012 season won't begin well for the Broncos as they get beat on their own field by a pumped-up Steelers team. The lack of comfort between Manning and his receivers will be the ultimate downfall in Week 1.
This could be a potential NFC Championship Game matchup as both the San Francisco 49ers and Green Bay Packers will boast two of the top teams in the entire league.
While Green Bay will do the majority of their damage during the season on offense, the 49ers are a defensive-minded team through and through. Whichever weaker unit gets beat first—be it the Packers defense or the 49ers offense—will likely decide the outcome of this game.
One really intriguing matchup will be between Patrick Willis and Aaron Rodgers. As the two best at their respective positions, you can almost guarantee that they'll be after one another from the very first possession.
Final Score: Packers 24, 49ers 21
As good as the 49ers are, the Packers are playing in Lambeau Field on opening day and that will be tough for San Francisco to overcome.
This opening night game on Monday Night Football will give an early preview as to who will likely be the favorites to win the AFC North. Of course, you can't forget about the Pittsburgh Steelers, but I do believe that both the Cincinnati Bengals and Baltimore Ravens will be better than Pittsburgh in 2012.
This is a matchup that was rather intense during the 2011 season thanks to the emergence of the Bengals as a legitimate team in the AFC. Even though Baltimore won both games last year, they can't take this opening game too lightly.
Baltimore will likely boast one of the best defenses in the league again. However, the duo of Andy Dalton and A.J. Green may be too much to handle with a full offseason to work together.
Final Score: Bengals 24, Ravens 21
This will be a hard-fought contest that will result in a great start to the NFL season. Dalton will prove just how clutch he is with a late game-winning drive to give the Bengals some hope this season.
If you're a fan of Indianapolis, you were probably hoping that the Colts would begin their season with the Jacksonville Jaguars or some other cupcake team. Unfortunately, Luck gets one of the better defenses in the league to start his career.
If Luck wins this game, it could be the beginning of an extremely special season and career for the rookie quarterback.
Final Score: Chicago 24, Indianapolis 10
As great as it would be to see Luck begin his NFL career with a win, he is going to be on the road against one of the better overall teams in the league.
Don't worry Colts fans, it'll get better quick.
You can bet that the Pittsburgh Steelers are going to be motivated and aggressive every single time Tebow steps on the field. You know they haven't forgotten what Tebow did to them last year, and that will cause this team to play at 110 percent all game long.
Neither offense is likely to put up many points during this matchup, and we could actually see the defenses combining for more points than the offenses. The deciding matchup in this game might actually be Darrelle Revis vs. Mike Wallace (if he is still on the roster).
Whoever wins that individual matchup will likely help propel their team to victory.
Final Score: Steelers 24, Jets 13
It's simply too difficult to trust the quarterback combination of Tebow and Mark Sanchez in a matchup like this. Throw in home-field advantage for the Steelers and you have an easy marquee win for Pittsburgh.
It's been nearly two years since Peyton Manning and Tom Brady squared off in a regular season game, and this matchup brings a whole new era to the rivalry.
Manning will be with a new team, and at this point in the season, he should have a pretty good feel for the Denver Broncos offense. Depending on how the young wide receivers on the roster develop while under Manning, the Broncos could sport one of the most potent offenses in the league.
Of course, they'll need to be potent to keep up with the offense that the New England Patriots will trot out onto the field. There may not be a more dangerous offense in the league than New England with Wes Welker, Brandon Lloyd, Aaron Hernandez and Rob Gronkowski.
One aspect of this game to watch closely is the impact that Denver's defense has on the game. This is one of the more underrated units in the league, and if they can consistently pressure Brady, it could be the deciding factor in the game.
Final Score: Broncos 28, Patriots 24
This is going to be the first game of the season that Manning rallies his new team on a late drive that results in a victory. It will show the rest of the league that the Broncos are a legitimate contender.
Cam Newton. Robert Griffin III.
Can anyone say "exciting"?
Over the past few months, these two quarterbacks have been compared time and time again. Well, in Week 5 we'll get to see just how similar their games truly are. Both quarterbacks have huge arms to go along with the ability to make plays with their feet.
While the Carolina Panthers may have more weapons on offense, the Washington Redskins have more weapons on defense. The game will ultimately be decided by the talented quarterbacks who lead the team, and whichever one can make the fewest mistakes will come away with the win.
Final Score: Panthers 27, Redskins 21
If these two teams were to meet later in the season in Washington, I think Griffin and the Redskins would come away with the win. However, since Griffin will still be adjusting to the NFL game, he'll be the one to make more mistakes.
What more could you want in a game than two of the most impressive quarterbacks in NFL history playing against each other? In all honesty, there isn't much better.
Both Drew Brees and Peyton Manning will get plenty of opportunities to make plays during this game, and it wouldn't be a surprise if both players had close to 40 pass attempts during this game.
What could ultimately decide this game is the play of Jimmy Graham. The Denver Broncos simply don't have a defensive player that will be able to slow down the New Orleans Saints' premier target.
If Graham can put together an impressive game and stretch the defense of Denver, the Saints will have a great chance to come away with a win on the road.
Final Score: Saints 34, Broncos 28
This will be a really exciting game for the NFL fan. Neither Brees nor Manning will make many mistakes, but look for Graham to have a huge game and be the difference in a victory for New Orleans.
There is nothing quite like a player returning to his old stomping ground to take on his former team.
This will happen in Week 9 when Mario Williams returns with the Buffalo Bills to play the Houston Texans. What will make this matchup so incredible is that both of these teams look poised to make a deep run in the playoffs this year.
What makes it even better is that Williams will likely decide the outcome of this game. If he can be an absolute force on defense and terrorize his former team, the Bills will come away with the victory.
However, if the Texans can neutralize Williams and keep him out of the backfield, the Texans offense should be able to produce some points.
Final Score: Texans 28, Bills 24
Home-field advantage is the key for Houston here, as they get a much-needed victory over the Bills following their bye week.
You can bet that the Chargers secondary is going to want to get physical during this game with Jackson, so the key player in this matchup is going to be Tampa Bay's other receiver, Mike Williams.
With San Diego paying so much attention to Jackson, Williams is going to need to have a big game for the Buccaneers offense to put up the points to keep up with the Chargers.
Final Score: Buccaneers 27, Chargers 20
It usually isn't until about Week 13 that the Chargers start making their playoff push, so they'll have difficulty slowing down Jackson on the road and will lose this game.
There is no doubt that the Green Bay Packers are going to desperately want to beat the team that took them out of the playoffs last year. You also know that as the defending Super Bowl champions, the New York Giants are going to have a massive bull's-eye on their backs all season long.
What will ultimately decide this game is the amount of pressure that both of these defenses are able to get on the quarterbacks. At first glance, the nod would have to go the Giants and their defensive line that includes Jason Pierre-Paul and Justin Tuck.
Final Score: Giants 24, Packers 23
Much like their regular season matchup last year, this game is going to come down to a late field goal. However, instead of the Packers winning, it will be the Giants.
There may not be a more exciting quarterback matchup than Michael Vick and Cam Newton. Both quarterbacks can make plays with their arm and legs.
Expect plenty of big plays when things break down. Neither of these defenses should be considered "elite," so the chances of a shootout taking place on this Monday night game are very good.
The winner of this game will be the team whose quarterback has the most yards on the ground.
Final Score: Panthers 23, Eagles 20
I think the Carolina Panthers are going to surprise some people this year. With a win this late in the season, they'll keep their playoff hopes alive.
Few teams truly despise each other as much as the Pittsburgh Steelers and Baltimore Ravens do. Their second matchup of the season could very well begin deciding which team will stay home for the playoffs in 2012.
Look for defense to be the name of the game. While both offenses have the potential to be potent, the truth is that both of these teams are defensive at their very cores.
It's going to be a brutal matchup with plenty of huge hits and probably numerous shoving contests after the whistle. One thing that we can be certain of in this game is pure hatred.
There simply isn't any love between these two teams.
Final Score: Ravens 16, Steelers 13
Like I said, this is going to be a defensive battle that will result in a low-scoring game. With this loss, the Steelers will find themselves needing to win their remaining games to get into the playoffs.
The Green Bay Packers and Detroit Lions have renewed their intense rivalry after their Week 17 shootout that resulted in a 45-41 win for Green Bay.
These are two of the best offenses in the league, and the star power on both sides of the ball is simply incredible. Of course, it all starts with Aaron Rodgers and Matthew Stafford for both of these teams. Rodgers and Stafford are easily two of the top quarterbacks in the league.
This game is going to come down to whichever defense is able to get a stop first. Considering this is the second matchup of the year between these two teams, look for the Packers' defensive coordinator Dom Capers to have something special worked up for the Lions.
Final Score: Packers 28, Lions 21
This game will come down to a late drive by Rodgers. With the NFC North divisional lead on the line, Rodgers will come up big to get the win for Green Bay.
The Atlanta Falcons and Carolina Panthers have quietly put together quite the rivalry over the past few seasons. With both teams likely to be in contention for the NFC South crown, you can bet that this rivalry will be on high alert during their second matchup of the season.
The key matchup in this game will be whoever the Falcons start at middle linebacker trying to slow down Cam Newton. After his impressive rookie season, Newton should take a huge step forward in his development, which should be scary for the rest of the NFL.
Don't be surprised if the winner of this game finds themselves in the thick of the playoff picture in the NFC.
Final Score: Panthers 31, Falcons 24
Like I said earlier, the Panthers are going to surprise some people this year. This late victory will put them in sole possession of a wild-card spot for the 2012 NFL playoffs.
This is a grudge match of all grudge matches. These two teams hate each other more than any two teams in the NFL.
While the battle is always intense when the Chicago Bears and Green Bay Packers meet, the intensity seems to reach a new level when the game takes place at Soldier Stadium. Throw in the fact that it's a late-season game that could have major divisional implications, and you have the making for a fantastic game.
Final Score: Packers 17, Bears 16
Whenever these two teams meet, it's always an ugly battle. This game will be no different as the cold and possible snow will keep the offenses at bay.
Whenever you have one of the top offenses in the league against one of the best defenses in the league, you are going to get a hard-fought and exciting football game.
While the players on the field may be fantastic, the coaches roaming the sidelines may be even better. Bill Belichick and Jim Harbaugh are two of the best coaches in the NFL, and two of the better coaches at putting together a successful game plan.
The winner of this game will likely be the team that executes their game plan the best. For the San Francisco 49ers, that will be running the ball and keeping it out of Tom Brady's hands. For the New England Patriots, it will be putting loads of points on the board in a hurry.
This game could be an early Super Bowl preview.
Final Score: Patriots 21, 49ers 13
New England gets the nod because they're at home and their offense is just a hair better than the 49ers defense.
With the signing of Matt Flynn, the Seattle Seahawks added a legitimate franchise quarterback to go with Marshawn Lynch and a talented and young defense. They appear ready to make some noise this season.
This late-season matchup with the San Francisco 49ers could very well decide who will wins the NFC West this season. Both teams love to move the ball on the ground, so you know this is going to be a game won between the trenches.
With that said, the linebackers in this game are going to have a huge impact. Considering the 49ers boast two of the best linebackers in the league in Patrick Willis and NaVorro Bowman, they have to be the favorites in this game.
Final Score: 49ers 19, Seahawks 17
As much as I like Seattle, especially at home, the 49ers have the better run defense and should be able to slow down Lynch enough to come away with the win.
This season finale for the New York Jets and Buffalo Bills will decide who finishes second in the AFC East and which team ultimately makes the playoffs.
This game is going to come down to pressure on the quarterback and who wins the ground game. With players like Mario Williams, Marcell Dareus, Fred Jackson and C.J. Spiller, the Bills will have the advantage in both of those aspects of the game.
Final Score: Bills 24, Jets 13
The only way I can see this game changing is if Tim Tebow is the starting quarterback by this point in the season. If that is the case, all bets are off. Tebow can do anything.