There would be countless fantasy settings, allowing me to run Ravenloft in one spot, Gamandria in another. It would have modern settings, historical settings, etc. In order to justify strikingly different physics in genres, I may incorporate some kind of belief based physics (whatever the predominant world view in a given place is governs what is possible and impossible). Alternatively I may get more specific and have the genre physics be the product of local gods.
While the more advanced societies might have quick means of travel allowing easy shifting from one campaign setting to the next, I am thinking of using portal gates for the less advanced ones. However I want to play around with them more, making them crucial sources of power. If they are two-way portals, they might also pose a danger to those near them. But I could see a potentate establishing control of a gate, fortifying it and using it to acquire knowledge, resources, etc. Whole trade system could be oriented around these gates depending on where they lead.
I think in order to allow for the most possible genres and settings there would need to be a pretty flexible and open cosmology (which is why I initially leaned toward physics and reality being somewhat governed by beliefs). It would be difficult to have an overarching cosmology that gave me the ability to have both Ravenloft and 2001. But I do like consistent and thorough cosmologies so I plan to think about this aspect a bit before reaching a final decision.
These are my early thoughts on the subject at least.