Well, whether you are awake or asleep, it's still "the simulation", but that's getting into semantics.
Anyway, yes, that's what I'm worried about - either sewer gators or zombies that get displaced during the accelerated simulation during sleep, or else just plain people having basements that connect directly to the catacombs, so when they go down to the cellar to grab some wine, they happen to walk into sight range of a zombie who chases them upstairs. Then that zombie who happens to be in a place he isn't "supposed to be" will just keep doing some periodic aimless wandering, and happen to walk out into the streets, and start eating the brains of the random villagers on the street, potentially killing someone important while your character is doing something totally unrelated.
This was one of the problems in TES: Oblivion, as well. Some characters would hang out at the docks, but mud crabs would randomly spawn at the waterside, and occasionally, they'd manage a kill on a named peasant character, and potentially automatically fail any quest those characters were associated with. There was even one noble who made weekly trips from one town to another with a single bodyguard, and if you happened to be near her path at those times, monsters could spawn near her and manage to kill her without you ever knowing she or the monsters had been there.
Having some sort of "solid barrier" like having the cities themselves being a different "area" that has a area transition door so that creatures generally cannot spawn inside a city makes sure those civilians and monsters stay separate, so that quest-participants stay alive.
In DF, of course, few of those procedurally generated characters have any importance at all that we, as players, do not assign to them (although one can always hope that somewhere down the road, the random peasants will start getting procedural personalities that actually manifest in their daily schedule and dialogue), and DF has a very definite "Life is Cheap" mentality, but it would be nice if, after buying a house in the city, you wouldn't have to immediately clean out the sewers in the area around that house or else have all your neighbors die of sewer gator attacks.