Fallout – Can you kill all non-quest NPC’s permanently

One option would be via a Mod. A quick scan of The New Vegas Nexus turns up Gore Tweaks, which promises to remove the more excessive dismemberment.

Alternately, if the .ini works intermittently, make sure you're editing the Steam/steamapps/common/fallout new vegas/Fallout_default.ini - When you launch the game from the launcher, it will reset any other settings to the values from that file. That may not fix it, as it's not a tweak I'm familiar with, but it's certainly worth a shot.

No.

There is a clearly delineated "Point of No Return", whereby setting out upon the final quest requires you to explicitly tell an NPC that you'd like to do so, from which point you can no longer explore the Wasteland, and once completed, the game has an ending, from which point, you can't continue playing. While this point is fairly obviously telegraphed, if you happen to not see it coming, the final quest involves returning to the Hoover Dam, after completing quests involving President Kimball.