I ran a long running game, Scions of Nathas using the Ars ruleset in a non-canon setting and it worked fine.
The games wiki can be found here(http://scionsofnathas.pbworks.com/w/page/15312850/FrontPage) if anyone wants to plunder spells, items, maps, races, background, inspiration, etc. We've long since stopped on this game so happy to see it be of use elsewhere.
With a change of setting we got rid of almost everything from the Mythic European setting, including the Order of Hermes itself. I replaced houses with classes which were slightly more mechanically defined (in rules terms each class got a few virtues and flaws for free, which were often quite defining for how they worked). We kept the latin names of the arts because I honestly couldn't think of a better way of doing it without inventing a conlang and I'm too lazy for that. We did ditch the in game use of Latin though.
We also got rid of Faerie, Divine and Infernal realms as they didn't really fit the setting. This did have the unintended consequence of making it really hard to botch magic since the PCs would never have negative realm penalties and this is probably one of the few things I'd want to take a hard second look at if I re-did the setting, probably going for more of the route used here in the Tablelands. One of my aims in ditching the Divine/Infernal in particular was to give my players more agency in the morality of their decision making by removing the objective endpoints at either end of the moral spectrum. My players would have to decide what was good or evil themselves, rather than having things, areas and people be coded by realm.
I think the Tablelands, albeit functioning more as a sandbox than a strict setting lacks a social framework for the PCs to fit into. In Ars Magica, the order and the society of Mythic Europe envelopes, constrains and supports them, giving the PCs a sense of who and what they are (and do), even if defined but their exclusion from that society. In the Scions of Nathas game, I was deliberately creating a campaign rather than a sandbox setting, so the PCs were exiles from another land, placed in charge of thousands of refugees, hurled (via portals) to a new world. They were constrained and bound by the society that they themselves were in charge of, but at the same time, all the social structures they had were carried from their own backgrounds and could be freely changed if they wished. Essentially my players had carte blanc to do whatever the hell they wanted and no one could stop them, they were constrained only by their moral responsibility to the people they were pledged to protect. This provided a framework for them to work together, and gave them goals at the start of the game (namely, protect the people, set up settlements, find food/water/shelter, explore the surrounding lands, meet and deal with the locals, etc). Essentially, in the Tablelands, what do the PCs DO, and WHY? DnD solves this with the basic assumption that you are adventurers and this is your job, to go do heroic stuff. It comes with the assumption that the players will agree to accept the plot hooks the GM presents, no matter how dangerous, because thats what the PCs do. Ars Magica has a more subtle take, motivation is more about resources, curiousity and knowledge, with a hefty dose of management and protection of what the PCs already have (e.g. covenant, covenfolk, good relations with neighbours, etc). Scions of Nathas had social responsibility and the harsh realities of being refugees in a largely untamed wilderness (or was it.....). Why do the Tableland PCs do what they do?