I would have to also break them down by system.
for the PS3 it would probably be between Uncharted, HS, or GTAIV.
for the 360, either Halo 3 or GTAIV, i don't know enough about Mass Effect.
for the Wii, Zelda PH or Mario Galaxy.
I think GTAIV will be ALOT more than what many expect, and if I had to pick just one that'd be it.