Blood 3. It has to happen! It HAS to!
The Neverhood 2 (3?). Armikrog looks to be amazing and all, and I'm still ever-so-happy that it exists, but I'd give Doug TenNapel's left leg for the return of Klaymen.
One I know will never, ever happen, but holy shit what if it did: A sequel to the scariest horror game of all time. It was Amnesia almost a decade before Amnesia was a thing. The only game in existence that can make me hyperventilate with a single abstract sound cue and floating JPG. White Day: A Labyrinth Named School.
If only somebody could make a sequel that fixed the worst part of the game: Actually playing it. Scare-wise, White Day is a damn masterpiece, but the gameplay can be... rough. A lot of modern horror games owe a hell of a lot to White Day, and a new White Day could learn a great deal from its descendants in turn.
Also, Patrick really should get around to playing that game on Spookin'. The resulting GIFs could fuel this site for decades.
EDIT: Almost forgot Wappy Dog 2: The Wappening! (2 Wap 2 Furry-ous) (Wappy Dog 2: Wappiness Is A Warm Gun) (Wappy Dog Championship Edition DX) (Wappy Dog: Lethal Wappin')