At one point, the game developers (I think maybe Joel himself) gave a rough outline of what they wanted the game's plot to be.
The idea is that there are two competing factions, one led by the Duke, the other by Noah from Whiteriver. During the game the player decides to side with one or the other. The end game would be a boss fight between the player, and either the Duke or Noah.
I don't know if that is going to make it into the game at this point. Bandits aren't part of the Duke's faction (his soldiers are called Cassadores), and it looks like bandits are the primary focus for human NPCs.
If you don't want to wait for TFP, I have a series of modlets that do something like this. They use the NPCs from Xyth, and add a couple more factions (whisperers and vault dwellers), but the idea is the same. You do quests for each faction (or murder that faction's enemies) to build reputation, and eventually you're asked by one faction to wipe out the others.
If you're interested, this is the topic where I post my modlets - go to the latest post for details about the NPC specific ones.