If you're on PC you can make everyone killable. The only problem is that people like settlers always come back. I know this because I have a "Settler limit" in my games where if the number of settlers gets too high, I kill them all.
It's fun since it makes those MM quest so easy.
Anyway, yea, if you want to go all Enclave in the wastes, you're gonna need mods to do so.
Yup, been playing that way for a couple weeks now...this is the first fallout game that, IMO has little replay value (as it is now with no DLC yet)..
A few things like hacking and lockpicking, and starting a conversation with people, ruin replay for me...so now on my second playthrough, to make it interesting, I just kill everyone possible...nobody is safe around me..
I still (occasionally) do dumb fetch, and kidnap quests, but in the end, if they can die, all of them will...