Anyone ever wonder what the total population of Sanctuary has to be? I mean between the invasions, cults, plagues, random villagers wandering into monster infested caves it’s a miracle anyone is left alive.
I believe Maltheal wiped out 90% of the population.
Besides that the towns seem to have some kind of protective barrier on them.
This is something that bothers me every time someone brings up immersion, but I’ll try not to dwell on that, at least not in all the fiddle little details. However…
Supposedly Malthael wiped out 90% of life, later retconned to 50%. Of how many, I don’t think we know.
However, the population of humans still seems to be quite high, as long as we’re assuming cannibals and knights to be included in that (despite the world clearly not having enough infrastructure for either food or living spaces.)
In fact if we assume respawn is just a game mechanic and when a human is dead, they’re dead, and if it’s canon that the wanderer has been to each dungeon, the number of people they have killed through story events, overworld wandering, and dungeon exploration is surely enough to be considered genocidal in scope.
Not what you asked, but what I wanted to answer. 
Sanctuary is what you get when people with no imagination are tasked with writing the extended lore for a concept that was about a single town with a cursed church connected directly to hell.