Even without Nadal, the Big Three will face many tough opponents in a very deep tournament.
After strong play in recent months, several seeded players appear eager to break through in the year's final major. They all display power tennis at its finest: a suitable style to succeed at Flushing Meadows.
Do not be surprised to see one of these sleepers go under the radar, advance deep into the second week and raise some eyebrows along the way.
Juan Martin del Potro remains an elite player lurking for his opportunity to return to the discussion with the Big Four. He is arguably the next biggest threat to conquer a Grand Slam.
Don't forget, he has done it before. He upset the heavily-favored Roger Federer in the 2009 U.S. Open. Who says lightning cannot strike twice?
After the best win in his young career, he endured a year-long wrist injury in 2010 that took years to fully recover.
The Argentinean-- currently ranked No. 8, highest since his injury-- finally rekindled his old form. His wicked whiplash forehand has been clocked over 100 mph. His monstrous serve consistently reaches 135 mph and has topped out at 147 mph.
His past few months have been very successful.
He lost to Federer in the semis of the Olympics in an epic 19-17 third set, which lasted four hours and 26 minutes: the longest in the storied history of the event.
He followed this disappointing loss with a victory over Novak Djokovic to earn a bronze medal.
Weeks later, he advanced to the semis at Cincinnati before falling to Djokovic.
He sports a tremendous 45-12 record this season and has reached two major quarterfinals this year.
Yet, the U.S. Open is his best surface.
Expect del Potro to make a deep run in New York and have an outside chance for the title.
The new del Potro returning to his old ways incites fear into the field, especially in the established hierarchy of the Big Four.
After elbow surgery caused him to miss most of the 2011 season, Sam Querrey skyrocketed up the rankings this year from No. 93 to inside the Top 30.
The American has regained his form that once made him a Top 20 player and the future of American tennis along with John Isner. His imposing 6-foot-6 stature enables him to crush ground strokes and hold serve with relative ease.
Querrey is on a tear with several impressive results in a row. He won Los Angeles without dropping a set, reached the semifinals in D.C., beat Top 20 player Kei Nishikori in Toronto before losing to Novak Djokovic in the round of 16.
Currently, he ranks second in the U.S. Open Series Standings with 110 points, after Djokovic and ahead of Roger Federer.
In Wimbledon, the California native proved he belongs in elite company after defeating Milos Raonic in four hotly contested sets. He then lost to Marin Cilic in an epic 17-15 fifth set. He displayed incredible mental fortitude and the heart of a champion in defeat.
Querrey poses a threat to any player because of his raw power and shot-making ability.
He performs his best under the bright New York lights, making the fourth round twice.
Do not be surprised to see him advance even further this year.
Party like it's 2007, at least for Richard Gasquet. In that year, he achieved a career high rank of No. 7 in the world and reached the semifinals at Wimbledon. The Frenchman has rekindled his old form by playing his best tennis in years.
He defeated Top 15 players Tomas Berdych, Mardy Fish and John Isner in a row before bowing out to top seed Novak Djokovic in the finals. This was only his third appearance in the finals of a ATP Masters tournament and his first since 2006.
He has regained his confidence on hard courts with his balanced all-around game that lacks a true weakness to exploit. Many laud his picture-perfect one-handed backhand (ranking near the top in the ATP with Roger Federer and Stanislas Wawrinka)and his deceptive forehand.
Gasquet has reached the fourth round at the U.S. Open three times.
This might be his year to advance further.
On the topic of Stanislas Wawrinka...he gained a lot of confidence after a great performance in Cincinnati. He defeated David Ferrer, Kei Nishikori, and Milos Raonic before losing to compatriot (and fellow 2008 Olympic Gold Medal doubles partner) Roger Federer.
According to Yahoo! Sports, beloved commentator and former player John McEnroe claims Wawrinka's one-handed backhand is "the best in the game today," and "the most powerful he has ever seen."
The Swiss native meticulously crafts points from the baseline, often moving his opponent side to side only to finish with a punishing backhand. He is also credited with silky smooth touch at net.
Once No. 9 in the world, and currently ranked No. 19, many tennis experts believe his mental toughness has held him back from becoming a stalwart in the Top 10. Recently, he has made positive strides in close matches.
Wawrinka reached the quarterfinals at the U.S. Open in 2010.
He is on a mission to return to prominence and will pose a serious threat to a challenger.
Everyone is waiting for Milos Raonic's breakthrough in a Grand Slam. He came out of obscurity to make the fourth round in the 2011 Australian Open, but has not advanced past the third round in a Major since. The fast U.S. Open hard courts should change that.
With a booming serve that is touted as the best in the game, he is no easy out. In 2012, he has more aces and won a higher percentage of service games than anyone on tour.
The best Canadian player in over 10 years has come awfully close to a marquee victory; Roger Federer eked out two wins against Raonic in a decisive third set, one in a third set tiebreaker.
In Cincinnati, the 21-year-old overpowered top competitors Richard Gasquet, Marcos Baghdatis and Tomas Berdych before losing to Stanislas Wawrinka in the quarterfinals in the third set.
Raonic, who achieved a career-high No. 15 in the world, is Tennis" href="http://sports.nationalpost.com/2011/01/24/real-deal-raonics-rise-the-stuff-of-legend/">viewed as the future of tennis, but can definitely make an imprint on the present. He has all the tools to advance deep into the second week.
It is aboot time the boisterous Canadian faithful have a reason to cheer in New York, eh.
After reaching the quarterfinals at last year's U.S. Open, John Isner has high expectations for this year's tournament. He followed up a strong hard court season in 2011 with a great 2012 season, where he has defeated Roger Federer, Novak Djokovic, and Jo-Wilfried Tsonga.
Overall, he has compiled an impressive 36-15 record this year.
For the first time, he entered the Top 10 in the ATP rankings in April and emerged as the top American contender.
The 6-foot-9 Isner possesses one of the top "one-two" punches in the game; he utilizes an overpowering serve that looks like its coming out of a tree, followed by a deafening forehand.
Because of his gargantuan size, he is nearly impossible to pass or lob at net. He has improved his return game and defensive prowess in recent years.
He has performed extremely well during the summer. He won Newport, lost to Andy Roddick in the semifinals of Atlanta, reached the quarterfinals in the Olympics before losing to Federer, and beat Milos Raonic before Richard Gasquet defeated him in the semifinals in Toronto.
As the next American hope, Isner faces a lot of scrutiny and pressure to perform in front of the home crowd, but possesses a great demeanor that will serve him well in New York.
He has all the skills to bring excitement back to Arthur Ashe Stadium and reach the semifinals.