We have been going over this for quite a while on the Steam forums. The devs have not really tried explaining what the problem might be, they might not even know. But the AIs and such only spawn around where you are. You can set the population in the city down in the options though, and it should help on the performance. For me it did not seem to do much one way or the other though.
I am pretty sure you could send your dudes across two separate districts and the game would still render entire areas along with every single NPC from what I've seen.
Seeing as this is a Unity game couldn't someone decompile the game, disable the NPC spawns, reduce the enemy spawns to like 1 or something and check if the performance improves? Maybe even disable the AI but it would probably be easier to just set the spawns to 0.
I wonder if the fog of war could also be disabled in order to check what else the game does. I wouldn't mind giving this a shot myself but I'm not experienced enough with these things.
All of that should be possible, even without decompiling. Its possible to mod the game now, and I am pretty sure that using this I should be able to chose to just delete all NPCs, I guess it might also delete all enemies, but there should be ways around that, and there should be spawn points, which can be deleted as well.
Been a while since I have modded the game, I recently tried changing the rendering mode on the games main camera, but it did not seem to help. But the in game option to reduce the population in the city should help give an indication of whether it would help to remove all the NPCs.