If reputation was added tomorrow and nothing else was changed, it wouldn't change much. Those who pk blindly are often fighting builds designed for fighting. They don't need to travel in safe cities or have anything to do with npcs. Such builds are backed up with trader/crafting builds that provide the fighters their items.
Even if every random pk got -10000 rep in every faction they might just get randomly killed by BoS, unity and patrols but that's it. It's not like those patrols would be assaulting their bases or appearing in their controlled towns or encounters.
So if alting was somehow cured, players wanted to play just one char and this char cannot randomly kill everyone if he wants to trade with npc traders. He could join in a faction that has shopkeepers and kill its enemies and this would be totally okay. If this npc faction was also the only place to craft certain hight tech gear, even better.
While I agree that they would be safe in their homes / bases, it would still discourage a lot of the Newb Pking. Admitedly my experience in this game is still as a newer player, but I don't think a lot of Pker's would want to fight every patrol they come across just to kill the occassional newb they can find. Even if they can take out entire patrols of NCR / Rangers / or whatever by themselves, it would just become annoying for them to constantly be attacked on site, at least for me it would be.
I find it pretty rediculous right now when I have a random encounter with Rangers and some brahman, and while trying to capture the brahmin another wastelander enters the ecounter, shoots me in the back, and loots my things all the while the Rangers stand there and do nothing.
Why would the rangers stand there an allow somoene to be slaughtered? I don't think so, for me it totally takes away from the Fallout atmosphere.
Even better would be if they automatically added a bounty on Pkers for each PK, this would discourage PKing even further, due to the fact that it would give other players a reason to kill said Pker for financial gain.
It wouldn't have to be a lot, but for each mindless PK the PKer would be racking up a bounty that would eventually make it worthwhile for others to want to collect on it.
As I stated already, as of now, the Game enourages anti social, bad behavior because there is very little discouragement not to do it. Alll it needs is a very tools to discourage it, but not make it impossible because obviously it should be possible.