Hen-shin a go-go, baby!
No seriously, I really don't know. Seen a lot of good suggestions here with Viewtiful Joe, Eternal Darkness, Wind Waker (tho the DS Zeldas are sort-of sequels to Wind Waker), Pikmin 3. I am also going to say Resident Evil 4, because RE5 doesn't do it justice.
But more than anything, I want a true sequel to Super Mario Sunshine, I really want to visit Delfino Island again.
I'm kidding! Relax!