Very difficult for me to decide...there's a lot of things to factor in...for example, Spyro the Dragon is the game that got me into games in the first place...Elder Scrolls IV: Oblivion got me into rpgs, and so on, so there's a lot of things to consider.
Right now I'm really enjoying Fallout 3. Overall for games though, I guess I like Skyrim the best. Sure, it's an imperfect game and leaves a bit to be desired, but it's probably the only game I've ever put 750+ hours into and still had fun with it. For that reason alone, I'd say that's probably my favorite.
This might change when I update my rig, I've got loads of games on my list I'll need to pick up!