If it's a named NPC, it's not likely. Only a small, small handful of named NPC's respawn.
I've killed Oliver Swanick (the powder ganger who won the lottery) twice. It does happen.
Oliver Swanick is a special case in that he respawns whenever you go through Nipton, and if you don't kill him he'll run off and die at the scorpion burrow. Otherwise Named NPCs should not, and some areas can be cleared of unnamed NPCs (like Nelson, Helios 1, Hidden Valley, Cottonwood Cove) as part of a faction based mission. In most other places unnamed NPCs will respawn, fiends, NCR and legion guards, even securitrons all do after a while.