The mystery plague that killed 99% of all the usual inhabitants of the world in which your story is set. Since NPCs are so hard to implement properly, the usual IF shortcut is to somehow make the world mostly deserted. Sometimes it's a literal plague. (Hello Planetfall). Abandonitis is hard to avoid completely, but try to make your world seem just a little lived in, even if there's nobody home *right now*. Finding an absent character's diary is a stock feature of Abandonitis.