You might be interested in what I'm setting to out build. I'm working on Archapolis, a city builder with real time traffic simulation and interior views of peoples homes (which you can customize/build yourself if you want). Very early stages of development still.
I created a path finding algorithm that can simultaneously path 300,000 units to random destinations at a comfortable frame rate. Units can choose from any of the shortest paths between two points (there are many in a grid), and from those paths, can also choose the path that matches any preferences they have.
I'm sure other people will suggest this, but does Cities: Skylines with mods kind of solve what you're looking for (admittedly missing the "runs in the cloud" aspect)? Some of the builds people make with mods in that game are incredible.
For a single-player game like this, instead of having it always running, I wonder if you could simply design the game in a way that the next state is deterministically calculated based on the time. So the next time you start the game, it loads the previous state + current datetime in order to produce the next state.
This would be prone to manipulation, if someone were to change their PC's datetime, but would give the illusion that it's always running without actually doing so.
That was the vision for SC5, if I rememeber correctly. Everyone was pissed off that the game required the servers and the servers would melt down regularly making it impossible to play.
I think people were more angry about the fact that the persistent connection was required for DRM reasons, rather than a bona-fide gameplay mechanic. It felt like EA being user hostile rather than some genuine attempt to enhance an aspect of the simulation like the GP is suggesting.
Yeah, thinking back more clearly, I think you're right. There was a promise of deeper simulation with the extra server capacity, but it ended up just being DRM and a pain in the ass.
I'd love a persistent, deeply simulated SimCity with cross-municipal boundary multiplayer elements.