What do you prefer in a campaign setting? Do you like a "kitchen sink" setting? Do you like specific purpose settings? Does it rely on generic vs bespoke RPG design?
First, some explanation of how we think about campaigns. There is the rules system, there is the genre, there is the campaign setting, and there is the premise.
I personally prefer genre-flexible rule systems. My favourite systems are Savage Worlds, GURPS and Fate which are all genre flexible with a different feel (pulp, gritty, and ‘narrative’ for want of a better word to describe Fate). But sometimes we’ll go with a targeted rule system like
Ars Magica; more on that later.
The genre is fantasy, sci-fi, space opera etc. The campaign setting could be Forgotten Realms, Star Wars, mythic Earth. Those are pretty common reference points I think.
The premise of the campaign is kind-of the elevator pitch for what the characters are or do, or the situation they find themselves in. For example, you could have a campaign in Eberron where the PCs are all members of
The Kings Citadel (Breland’s secret service). Or you might have a campaign where super abilities appear in the world and the PCs are some of the first people to gain them for some reason.
So - the answer to the question is largely ‘it depends’. For 95%+ campaigns I would run with one of my favourite systems, with 90% probably being Savage Worlds. The campaign genre and setting are usually closely tied together for obvious reasons, though you might do a bit of subversion like playing in the Star Wars universe but all based on a single planet with a more Wild West feel. Generally I like the campaign setting to be big and fairly all-inclusive as I can then focus in on the relevant bit while keeping a framework that the group are mostly familiar with. The premise is the most specific of course.
For some combos the balancing act is more tricky and all or at least most parts need to be aligned.
Ars Magica is the best example of this from my personal experience. The way magic works can be matched in other systems but the unique things with
Ars are how that then interplays with the troupe-style play, the way characters advance, and the constraints that mythic Earth puts on the mages. Take out any of those legs and the game starts to topple. But those combos are in the 5% since
Ars isn’t a system I would personally want to run or play all the time.