While I would be a happy camper with either Super Mario Galaxy (2), Wii Sports, Street Fighter IV, Uncharted series, Bioshock, Demon's/Dark Souls, GTA 4 (or 5), Batman Arkham series, Bayonetta, XCom, or any of the other candidates listed here in seriousness (bolded are my favorites out of those), there is one game that haunts this thread by not being released. A game that I feel would certainly have topped my list of most memorable games of the generation: The Last Guardian.
It certainly was one of my most anticipated games, and still holds that honor oddly enough. A real shame how this game went from an almost garanteed top 10 worthy game of the last generation to being either a running joke or one of the most powerful signs that modern (Japanese) game development is in trouble.
On a sidenote: we should defnitely also do a "best overlooked games of the last generation" thread. My nominees (off the top of my head): Trash Panic (Tetris with a Japanese twist and physics), Double Dragon Neon (that music, that cheese!), Kirby's Epic Yarn (that art and charm!)