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Yes unless something causes them to despawn, obviously death will do that so keep out the hostile NPCs and lava, but there also appears to be a cap on player spawned NPCs that can be in a certain area simultaneously, last I checked it was 20 in something like an 8x8 chunk cluster. When the cap is exceeded the oldest NPC despawns. This does not affect world generated NPCs but given that you don't intend to have any it's something to keep in mind.
There probably is a way to remove the cap by modifying game files as there didn't appear to be one during Early Access, but I haven't looked into that at all.
http://steamcommunity.com/sharedfiles/filedetails/?id=937878161
Some NPCs appear to have a greater tendency to roam about than others, at least town, village, and frontier characters seem to stay within the boundaries of their city, so you may want to look into that. Perhaps search for a world with a large city, remove it and use it as a foundation for your own city.
As for a custom world without NPCs, sure, but as mentioned above, when manually populating it the cap on player spawned NPCs will be the limiting factor.
Sorry for the speculative info, I above all suggest to do your own experiments, if you really want definitive answers you can try figuring out what the Developer's Bat-Signal is.