Like so often, my answer is Wing Commander. With proper sequel/finish for the story started in Prophecy, the fifth and final game (aside its independent DLC Secret Ops).
I'd also like to see a reboot of Myst, something like the spinoff Uru - set in same universe but otherwise unconnected to old games. They can keep making all the remakes they want, but I'd like an entirely new Myst game.