Suikoden VI. Needs to be made, end of story. In a world full of endless grinding RPGs, a new Suikoden would be a breath of fresh air. Also, Game of Thrones meets Pokemon, it would sell hotcakes.
While Shadow of the Colossus is not really a game that should have a direct sequel, I think another exploration-based "kill huge monsters" ICO game would be great.
Half-Life 3. As everyone else has mentioned. Even though I am like the 90th person on this thread to suggest it, it would just be that awesome.
Zone of the Enders 3. While the other titles were ok, and I had my problems with them, they were onto something really great with very agile and fliudly controlled Giant Robot battles. If they expand and improve this, I thing it could be a great game.