Resident Evil 5? I have personally beaten Resident Evil 4 on both GC and PS2 around... i lost track around 30 times, not to mention assignment ada and mercenaries...
Starcraft Deux! I have been playing the original for around six years, and during the summer I tend to spend 14 hours playing, 10 hours sleeping and only taking breaks to eat and excrete. Very hesitant, I tend to dislike 3D RTS's.
Diablo Trois! Basically anytime during a summer where I wasn't playing SC, i was playing D2.
BTW: I have personally run through two copies of Diablo II, 2 of the exppac, 4 copies of SC, 3 of BW, and my GC broke before my RE4 did -> after it broke I just got it for the PS2.
I'm currently wanting to play ODST, but I run through so many games, it's hard to say that any one specific game is the most awaited.
I'll have ODST in about 3 hours though, so I guess there's nothing I really have to have.
I can't wait for The Last Guardian, but in all fairness that won't come out until 2010.
I'm enough of a fanboi (well, fangrrrl I guess) of the Katamari franchise to be psyched for Katamari Forever, although having played the demo I'm feeling a little cranky at their continued abuse of interaction design.
Can't wait for Brutal Legend!
Really really can't wait for Ratchet and Clank: A Crack in Time!
Intrigued by Heavy Rain but not sure if it will actually be any good.