A harvest run is my favorite mode but the only differentiation between each playthrough is the random enemy spawn system. They all require 4 players and that can be difficult to find 4 good enough players to unlock the loot.
You could create some new Harvest Run modes that only require 2 and 3 players - like a rescue mode where you have to locate a missing 4th player and rescue them and get them safely to the end. A repair/scout mission where just two players go in with special backpacks to collect and carry the right parts to fix saferoom dispensers and place ammo boxes. Perhaps they go in against different enemies and have some special tools to help board up rooms.
Just some ideas that wouldn't require whole new maps that would REALLY expand the flexibility of the game.