The first campaign I am going to run is a low-fantasy apocalyptic survival campaign, taking place in a mostly medieval (rare magic) region. However, the setting allows for all tech levels, magic levels, psionics, and campaign genres to exist simultaneously (in particular if they occur on, say, different planets in different galaxies or something). Eventually, multiple campaigns in the same setting will begin to paint a dynamic and inter-connected picture that produces its own prompts for continuation. My hope is that if the players should finish a campaign (or their characters die) that they might start new ones in the same world (but involved in different adventures), who encounter the changes their previous ones made in the setting, etc. Although most of the setting is low-fantasy, I have a lot of higher-TL campaigns in mind as well (which will be connected in the game universe).
Having given myself a lot of latitude (read: Portals), even a campaign which poses an existential threat to a large portion of the setting will not seriously disturb the potential for expanding it. This is important, because the first campaign will be a kind of "sandbox" where the spread of The Crisis will be along trade routes, roads, etc. (so the extent to which the game universe is altered by it is largely up to the players and the simulations).
Although I'm primarily making this to play with some tabletop gaming friends, I am also a simulation enthusiast and some-time coder. There are coding and writing projects which naturally flow from making a project like this (for example, short stories; or scripts which instantly generate NPCs and encounters according to home-rolled tables which take care to work just as well using nothing but dice). To playtest for sessions with my friends, to refine the setting, to play with ideas, and just for fun, I will run a lot of "simulations" in the background of the world between game sessions. Those simulations will generally be posted here for the players to enjoy, and for my later use (as writing prompts, story ideas, records of the setting's unfolding exposition, etc.).