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I say Starcraft 2, Mass Effect 2, or Zelda Wii. As Mass Effect is the only one to come out yet, it's winning for me. Overall, I predict Zelda Wii. If Crysis 2 comes out this year, it might win. Same with Diablo III, but we all know that D3 is coming out in 2016, so I'm not going to count it. :P

P.S. Another strong contender is Mario Galaxy 2.

P.P.S. As other people have mentioned, there will be several GOTYs. Last year for me was Dragon Age, but everyone else said

"Uncharted 2 is teh best game evur. Ur just mad it's not on ur PC and u can't play it becuz teh ps3 is awesome and PC has no good gamezz. Lol Nurd fagget"

and yes, I do get that a lot. (No disrespect meant to ps3 owners (I am one myself) or Uncharted 2 lovers (I am not one). Just summarizing the general internet's intelligence level).