Another one I've thought of is a zombie apocalypse game. Starts out as a normal campaign and then someone (perhaps the PCs) starts a plague of undead by opening the wrong crypt.
At first the zombies would be typical Walking Dead/Romero zombies but then eventually as monsters are infected you could have more Left 4 Dead/Resident Evil zombies, especially as some mages try to "fix" things with unforeseen consequences.
Ideally it would be quite a lethal game as the PCs are infected and have replacement PCs come in to replace them.
Haven't done it because part of the fun would be the reveal, but it also violates my "player campaign buy-in".
Very similar to one I forgot I wanted to run - thanks for the reminder.
Players would be bought in.
First session is a flashback where the PCs are relatively low level and they open a crypt of undead horrors and get overwhelmed and all die.
Second session starts 25 years later. The children of those characters are the new PCs. Initial session, they are at the last bastion of civilization next to a huge blighted area the size of Texas. Their mission - go in and 1) retrieve or at least find out what happened to their parents 2) figure out what is up and hopefully stop the spread of this undead blight and 3) maybe, if possible, redeem their parents to history.
Theoretically they might find some glimmers of safety inside the blight; but otherwise it would be survival horror with a mission.
(I have also considered using Golarion and the WorldWound as that setting and saying "Demons" instead of "Undead").