Uncharted 2, no contest. One of those sequels that bests the original by so much on so many levels, that the minimal advancements made from then on in the following games never provide that same jump again. The level of polish in Uncharted 2 is great and, after that lame sneaking level at the beginning, the game is fun the whole way through. My second favorite game on the PS3 after Bioshock and one of my favorites of the entire 7th generation.
And while NSMB Wii, Arkham Asylum, Bayonetta and Assassin’s Creed 2 are all great candidates for runner up, I’d vote for Punch Out on the Wii for second place because it’s damn fun and I frickin love those games.