My vote has to be Street Fighter 4. The game single-handedly brought the fighting game scene back to life when it looked like there was no cure in sight.
Runner up: CoD4 Modern Warfare. Love it or hate it; this is the entry in the series that did so much for FPSs. The inclusion of an RPG like infrastructure kept people coming back to unlock things. Not to mention the great graphics, 60 fps, as well as a departure from WW2.
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There's no way I could just pick one, or even one and a runner up. I'd have to categorize it all because I'm not sure any one game was the best at everything or even the best at most things.
For instance I think Alan Wake created one of the best worlds and was extremely immersive but some of the times when it became more of an action game kept it from being fully #1 in all areas.
Then there's Bioshock and that was awesome in many areas, but there was also a lot missing. With no connection to a "real world" it felt, well, disconnected.
Skyrim is amazing as well but a lot of the game ended up feeling kind of sterile to me. I still spent over a hundred hours playing so yes it's amazing, but it just wasn't as inviting as Oblivion's world or Morrowind.
Dishonored was amazing as well, but it was extremely short and felt like it was clearly a game made to build a franchise on.
Etc etc etc...
"You shouldn't be asking HOW things are, given that we already know there is something..but rather WHY things are, as opposed to there being nothing."
I have to agree. An amazing experience, especially since I had never played a Half-Life title before giving this a try. In terms of stand-alone games that were my personal favorites, though, I'd probably have to give the nod to Bioshock, with Mass Effect and Oblivion close behind.