4e would seem to work very well with what I intended to do in terms of a homebrew. Essentially, a realm where humans haven't been around for millenia, not until the powers of a foreign land decide to start dumping their criminals, debtors, and malcontents there. Eventually, the ships carrying in new exiles from the motherlands stopped, and the descendants of the original exiles have been there for about one and a half to two centuries, building coastal cities but largely avoiding the interior of the continent and the native races. As originally planned, there are no kingdoms or large states, just regions where certain races gravitate and have a few small city-states and supporting communities or villages.
Instead of my own homebrew native races, I actually have an interest in the core races again from what I've seen of 4e, and the ancient empires of the Dragonborn and Tieflings will work rather well as the fallen empires of this land. It also fits with the backstory I had: until 150-200 years ago, humans hadn't been a part of this land for millenia... except now, it's because the last humans to inhabit this continent became the Tiefling race.
I'll probably dump the pantheon from the default, though. I have a few ideas in that respect. Humans will fall into one of two categories of either a monotheistic faith supported by the human cities and communities that directly support them, or the other more rural humans who will worship what the first group would consider a pagan god or gods. The ancient races native to the land (now the dragonborn and tieflings for 4e) have a strange, massively polytheistic religion that combines astrology with mythology - they believe each individual star represents a minor deity, and there are shrines spread out across the land to each (the locations of which match the positions of the stars in the sky during equinox.) They don't worship the individual entities within the pantheon, but they rather the whole pantheon in a "celestial" religion. This might be interesting to mix with star pact Warlocks as arcane counterparts to that religion, now that I know about them. I'll probably hold on to the "elf gods" for the elves, and halflings as nomadic traders will just adopt whatever suits them individually at the time. I'm not sure about dwarves yet. Monstrous races would have obscure or ancient forms of worship, some very Cthulhu-like.
So I'm well on my way to a homebrew campaign world, and it actually would seem that I can make it work in 4e pretty well, so now I'm adapting it more on occasion, as I learn more.