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Freedom Force is my personal favorite game of that decade.  I enjoyed the hell out it when I first played it.  It broke the "curse of the superhero game" that people don't even remember anymore, because there have been a ton of great superhero games since.  Most importantly the only other game remotely like it is the sequel, although I think the first game is better.  It's a really fun and amazing, one of a kind game.

If I were to pick most influential that is not necessarily my favorite it would probably be Wii Sports.  Minecraft is also a good contender, but it was released at the end of the decade and grew in popularity gradually, so it is more associated with the current decade.  Wii Sports basically defined the whole decade and generation 7 though.  It caused a major cultural phenomenon and even Sony and Microsoft had their own motion controls after a few years.

If I were to pick a game I really liked and was really popular it would be New Super Mario Bros Wii.  My family played that game for 500+ hours.  It was the first time I experienced multi-player 2D Mario.  And the Wii set a December sales record in the US the month after it was released.  It's such an awesome game in every way.