This is a tough one. SO many great games to choose from, from Halo 2 to COD4 to Mass Effect, all the way back to Panzer Dragoon Zwei and Super Mario World.
If I have to choose just ONE, I would probably choose World of Warcraft, simply because the game world is so imaginative and it still holds my attention pretty well after nearly 5 years playing it.
Still though, Halo 2 is my favorite game, I just don't think it's the best game I've ever played. The multiplayer though is just phenomenal.