Regular npcs will pop back up no matter how many you take out but there's a catch with some specific characters. Two of the ripperdoc vendors are actually permanently killable which might not be the best idea since you'll lose their services for good. Same goes for certain shop owners and quest vendors, once they're gone that's it no coming back.

Watch out though cause the game's got some limits, main story characters and kids are completely off limits won't even let you target them. Going on a rampage isn't really worth it since most npcs just respawn anyway but taking out specific vendors can lock you out of some pretty useful stuff. Maybe interesting to know that depending where you start trouble, you might get the police or local gangs on your case

not exactly the best strategy for long-term gameplay, especially if you're planning to use those vendor services later. The city stays pretty much alive no matter what but picking specific targets can definitely make things harder for yourself down the line