The Red Devils missed out on an historic 20th league title thanks to one Sergio Aguero kick of a football, and—despite their tendancy to start the season in lacklustre fashion—will no doubt be going all out for a win in their first match.
The line-up for the game at Everton could look somewhat different to that of last season, with manager Sir Alex Ferguson set to go for a slightly alternative approach this time round.
Here is a prediction of what Manchester United's starting XI might be for the Everton match.
GK, David De Gea: Obvious candidate for the goalkeeper slot. Anders Lindegaard statistically was as good as De Gea for much of last season, and while he provides excellent back-up, the 21-year-old Spaniard will always be no.1.
RB, Antonio Valencia: Given his form as a winger so far in 2012, it may seem strange for Antonio Valencia to be played at right-back.
However, the Ecuador international has also played well as a right-sided defender, and has all the attributes to do well in that position—he combined his 13 assists last term with 66 tackles and 29 interceptions.
To get the benefits from Valencia, and accommodate the other talented players in the squad, Sir Alex Ferguson may have no choice but to put the former Wigan Athletic star at right-back.
CB, Rio Ferdinand: He was controversially left out of England's Euro 2012 squad, but having the summer off will do Rio Ferdinand a world of good, allowing him to be fresh physically and mentally for the season opener.
Given he has a ton of experience and ability on his side, having now better adjusted his game to compensate for his lack of pace, 33-year-old Ferdinand will no doubt be an automatic choice for Sir Alex.
CB, Nemanja Vidic: Aiming to be fit for the match with Everton, captain Nemanja Vidic is the first name on the teamsheet when available for selection.
At the moment, he's poised to return against the Toffees, and thus is another automatic selection, especially given his partnership with Rio Ferdinand.
LB, Patrice Evra: Leighton Baines could well be a Manchester United player as opposed to an Everton one when this game kicks off, but even if he is, Patrice Evra looks set to retain his place in the team.
The 31-year-old left-back had a poor season by his standards in 2011/12, but there's no doubting the ability he has, and at the moment he is the club's best option in that position. Plus, he's a key player in the dressing room and a man his teammates want on the pitch.
CM, Paul Scholes: Having signed a new one-year deal back in May, legendary pass master Paul Scholes will play a pivotal role for Manchester United this season, with a pass success rate better than any other Red Devils player.
He won't start every match, but he'll certainly be included in the important games—and the opener with Everton being one of them, given how momentum will key to United psychologically this term.
CM, Michael Carrick: One of the team's best performers last season, Michael Carrick is another member of the Manchester United side who's place in the line-up is virtually assured.
His passing and vision matched Scholes' at times, while his defensive ability—90 tackles won and 79 interceptions made in the 2011/12 campaign—gives Scholes the license to be a true deep-lying playmaker.
RW, Nani: Portuguese winger Nani had a decent campaign for United last season, scoring eight league goals, making ten assists and hitting 68 key passes.
And at Euro 2012, his form has been even better, making two assists and hitting 13 key passes in the four games he's played. Given how Ashley Young has had a poor tournament for England, Nani will seemingly get the nod to start at Everton.
LW, Shinji Kagawa: How can Manchester United get the best from Shinji Kagawa without sacrificing other burgeoning talents in the team?
Given how well Danny Welbeck has played for England, it would be a big waste to play Kagawa in the trequartista role supporting Wayne Rooney up-front. Therefore, the best position to get the most from the Japan international as well as others in the team could be to put the 23-year-old on the left wing.
From there he could continue his assist-making ability—he made eight in the Bundesliga last season—and positionally inter-linking with the forwards to create attacking unpredictability, he could also get into good positions to maximise his finishing ability, having scored 17 goals in all competitions.
It's the position he played when he was at Cerezo Osaka, and it was good enough for him to score 50 goals from 91 games in three seasons at the club, and attract the interest of Borussia Dortmund.
SS, Wayne Rooney: It's a trait of his game that's been clear throughout his career, and even more so at Euro 2012.
Wayne Rooney is a forward who loves to drop deep and collect the ball, before linking-up with a strike partner and creating openings in the final third.
It's his best position, as it also gives him the space to hit his trademark wondergoals. Therefore, it could where Sir Alex Ferguson sees his future at United.
ST, Danny Welbeck: It's a testament to Danny Welbeck's ability that at just 21-years-old and having only been capped by England five times before Euro 2012, he was an automatic choice in all four games for Roy Hodgson.
Such is his ability and clear potential in attack, he'll no doubt he a starter for Sir Alex Ferguson this season. He'll start the match as the furthest player up-front, but it's a position he'll swap with Rooney and wingers as play progresses.
The Rest: Manchester United have a lot of good young players waiting in the wings, and it'll certainly be competitive in the squad this season, with the likes of Phil Jones, Chris Smalling, Jonny Evans, Rafael Da Silva, Tom Cleverley, Ashley Young, Javier Hernandez and potential new signings like Leighton Baines and James Rodriguez all vying for a place in the team.
All those players will certainly get game time, as will the likes of Ryan Giggs, Park Ji-Sung and Darren Fletcher.
However, it remains to be seen where players like Anderson fit into the system. If the Brazilian doesn't impress soon, he could be one for the chop. Either way, he's certainly a player who doesn't add much to the team, and could suffer the same fate as Michael Owen and Dimitar Berbatov.
Thoughts: Manchester United's line-up is a positive one, and certainly one which can challenge any Premier League team.
Pound-for-pound it isn't as good as that of Manchester City or Chelsea, and while United will unassailably finish in the top-three again this season, they will need a few of their players to have unexpectedly stellar seasons if they are to regain the Premier League title.