I've been cooking up an idea for a smaller style MMO with as few NPCs as possible. It'd take a large skill tree in which you can't possibly put points into everything so people have to specialize and work together. NPCs might fill in jobs while a player is offline like taking sales at the store or unattended crafting but all quests and rewards come from other players. Something unavoidable is that I think there has to be an end or else people either 1) can branch out and become so skilled they don't need other people or 2) stagnate. So after X real world days, an apocalypse happens. Plague, dragon attack, aliens, zombies, blight, pirates, whatever. If you win, you can rebuild and get a benefit before your next go around. If you lose, you migrate to a new place (generate a new map) and try again.
A small part of that sounds similar to the "asynchronous online" features of Death Stranding (one of my favorite parts of the game). I would love to see more games adopt features like them.