I think it would be good if there were just different levels of protection in each city, without any 9999 guards nor some weird gm interventions. It would be only obtained by different strength and quantity of guards.
So that cities from the south would be hard (Junktown), very hard (Vault City) and (relatively) almost impossible (NCR) to raid, and those cities could have call in some reinforcements.
There could be also some small areas like shops or pubs in north cities guarded by some weaker guards too (like spawn near modoc).
I also think that ordinary NPC citizens should have some basic combat skills and weapons, because it looks stupid when you get chased by a bunch of NPC with their fists, obviously doing no damage.