Not Modern Warfare 3.
There are reasons, but I don't really feel like going into them here. Maybe when a MW3 specific thread comes up I'll go post my thoughts.
Beyond that, I'm waiting to play Skyrim and Battlefield 3 before I make my final decision, but right now Portal 2 has lived up to the hype and deserves mention as a serious front-runner. However, if Bethesda has learned from Oblivion, and has kept the things that worked brought in a better story, plus all the other things they have already shown they've changed, I think Skyrim is the game to beat.
Also, I'm putting in a dark horse mention for the PC VERSION of The Witcher 2. I don't really have a lot of confidence in their Xbox 360 port, which isn't out yet. It's a very deep game, but does have some minus points on it. At the very least there won;t be a better PC game this year.