Outside of the big three, the likes of David Ferrer, Del Potro and Jo-Wilfried Tsonga will be favored to pounce in case of a slip-up.
Spanish world No. 5 Ferrer, a semi-finalist at the French Open and quarter-finalist at the Australian Open and Wimbledon, has a best New York finish of the semi-finals in 2007.
World No. 8 Del Potro is still to back-up his 2009 US Open triumph after missing the 2010 season with a wrist injury.
Tsonga, the world No. 6, was a Wimbledon semi-finalist for a second successive year in July, made the last eight in New York last year, his best performance in four visits.