My setting is post-technological fantasy; the magic is using remnants of extremely advanced technology but the inhabitants of the world don't see it that way or think of it that way. Magic and technology are not separate and co-existing things, they are the same. I aim for a classic fantasy tone, e.g. there are no blasters, but there are wands. To achieve that, I replaced the usual three realms with five: earth, water, life, self, and aether, reflecting different sources and types of power. Dwarves inherently use earth magic (to varying degrees but all of them have it), to be aware of their environment, to shape it, to improve their crafting, etc. Elves (and sprites, dryads, etc) inherently use life magic to work with living and organic things. Naiads use water magic. So, the races are customized (I'm using standard RMU cultures though), the professions are customized. I've customized or created 58 spell lists (basing them on RMU lists where available but also RM2 and RMSS lists as well as entirely new lists) and still have some I'm planning to add.
Early on, I was largely using the RMU professions, just letting the characters pick their spell lists from any lists in the realm. I think it started working better after I made my own professions and narrowed down the list of possible spell lists. For example, the monk is a discipline-based magic-using combatant, and you can use it to handle a more heavily armored weapon-using combatant with magic, but it was better when I made a separate profession for that. It helps that RMU has rules for creating professions, it's pretty easy in fact. Tweaking spell lists is fairly easy, too. Making new lists is more work, if you are doing your due diligence to try to balance them against existing lists, but if you are willing to mine all the existing editions and sources, you have a lot of material available to start from.
Our RMSS game (likely switching to RMU "soon") is more classic, not much customization. The setting has some other influences since the GM originally ran a campaign in the same setting (with different players) in D&D before switching to RM.