Super Mario Galaxy 2 is a contendent, as it holds one of the greatest score of all time, followed by Mass Effect 2, Red Dead Redemption, God of War III
But we hadn't seen yet how Gran Turismo, LBP2, Fable III, Halo Reach or Metroid Other M will be. Even Donkey Kong, Epic Mickey or Kirby could be contendents, so we'll see.