The golden rule of sandbox content creation is simple- if you don’t need it for the next session, or you’re not having fun creating it, then don’t bother with it. You don’t need to do it. A game that leaves you drained and exhausted is a game that’s certain to fail. Running a sandbox is meant to be fun for the GM too, and you shouldn’t force yourself to do preparation work that isn’t satisfying or entertaining for you.
In the terms of exploration-based adventures, such actors might approach or interact with the PCs in regards to their ultimate goals. In regards to antagonists inhabiting dungeons, it's inevitable that they will not be content to wait about in Room 5 for a band of adventurers to bust in. Intrigue-based adventures are the most complication of all, and need a major source of conflict between the actors which can change and react to the PCs' interference.Actors are different. They have a motivation or goal that is likely to intersect with the players, and they aren’t simply reactive denizens that respond only after being provoked. The witch-lord of Lost Badiye doesn’t just sit on his royal stool and wait for heroes to come stab him, he’s trying to whip the unruly denizens of the ruined jungle city into a military force capable of breaking the Lokossan border guards and opening the way for his Night Man allies. He’s going to be taking actions appropriate to that goal, and if the PCs start slaughtering his potential cannon fodder, he’s going to be inclined to do something about it.