I have to say this thread turned out way better than I would have ever imagined. Building upon the many ideas and tips that I got here, I have a rough outline for a setting and campaign framework, that I think could work really well.

The landscape is based on the Baltic Sea and the surrounding lands of Northeastern Europe, while the culture, technology, and visual style is based on the 14th century and includes also Byzantine and Mongol influences. The people are all effectively human with only some aesthetic adjustments to make it all feel a bit more otherworldly. It's a region and culture I've never really seen used in fantasy. One that is in many regards very similar to the familiar Viking settings, but at the same time also somewhat exotic due to the Asian influences that are bleeding into it.

Magic and religion is so deeply interwoven that it is basically the same, a form of pantheistic mysticism. The universe is a single plane in which everything is infused by a universal animating life force. Studying this force through mystic meditation and esoteric rituals allows people to manipulate it and cast spells, but an ordinary mortal mind is not meant to handle such an unfamiliar way of thought and perception. Both the knowledge and casting of spells drives people insane, which can be countered by the study of various mystical traditions that let a mystic make sense of the eldritch chaos in their thoughts to keep their minds and humanity intact. But even study of the tradition only reduces these mind altering effects, which makes mystics much more susceptible to certain supernatural phenomena that can shatter their minds much faster than those of regular people. They are especially vulnerable directly after casting spells and can destroy their minds by using too much magic in a short time. (This is a straight up adaptation of the traditions and the corruption system of Symbaroum.) But even to the ordinary people, these mystical philosophies are a source of spiritual strength and comfort by visualizing the universal life force as something less abstract, like the moon or fire.

Mystics are the dominant NPCs of the setting. Be it as priests or as independent sorcerers and witches. They pay a lot of money for unknown magic items, ancient tomes, or the notes of other powerful mystics who have made significant discoveries and breakthroughs. On the one hand it gives them more magic power, which translates into political power, but on the other hand it also is very important for them spiritually. Of course, being a Dark Fantasy setting, they are all loath to share their secrets and will never willingly let them fall into the hands of their rivals. To some degree they are all corrupt, even the pacifistic priestesses of the Mysteries of Life. They might not harm you or set you up for certain death, but they will be economical with the full truth and exploit their pawns for their personal gain.
In this environment, the players can take the role of treasure hunters, mercenaries, thieves for hire, or even temple enforcers, who search for ancient artifacts and tomes, protect them from theft, or steal them from rival factions. It doesn't have to include outright murder by any involved party, but that's always a possibility.

The life energy is not distributed evenly and people are most comfortable in regions where it exists at relatively low levels and few supernatural phenomena occure. In contrast, spirits are most comfortable in regions of very strong life energy where nature can behave in very weird ways. Spirits and mortals tend to not get very well along with each other and regions that are home to large numbers of powerful spirits are effectively uninhabitable. Minor spirits lingering in the woods beyond the fields don't tend to be much of a problem, though.
Unfortunately for everyone involved, the concentrations of magical life energy are not permanent or stable. Like the weather, minor fluctuations occurre, but generally it's very similar from year to year. But in the long run on the scale of centuries, like the climate, these patterns shift. Sometimes this shift can happen in a matter of just a few years, making large regions effectively uninhabitable. As a result, ruins are scattered all over the world, the remains of cities and towns that had to be abandoned with its population rebuilding elsewhere or integrating into neighboring peoples. There are also cases where there are surges in magic that last only for a few days or weeks, during which the effect on the local inhabitants can be devastating.

While commenting on a post at Monsters and Manuals, noism pointed my at an older post about how The Revenant is actually taking place in a post apocalyptic setting. I've not seen the movie but looked up the scenes with the natives, who really are the last scattered survivors of a megaplague that wiped out civilization and brought an end to the world as they knew it. It's Canadian Mad Max. Reminded me quite a lot of Dead Man mixed with Apocalypse Now. (I also have to say, the music is the creepiest horror soundtrack I've come across so far.) I think this is exactly the way I want to portray areas that have recently been overtaken by the Weird. When a region can no longer sustain cities and towns, sometimes it happens so quickly that villages are cut off by the encroaching wilderness and try to stay put in the relative safety of their homes. Sometimes people are left behind in the evacuation, or they refuse to flee to safer lands. After a couple of years, their conditions are dysmal and they either have to make pacts with powerful spirts as their protectors or face certain extinction.
During migrations, some stuff is always left behind, especially when it was hidden and its hiding place not known to many. Paranoid sorcerers and witches often leave behind stashes of very valuable artifacts and it can take decades or even centuries before someone deciphers the clues in the scattered remains of their notes, long after their homes and lairs have been swallowed up by the weird wilds. That's a job for treasure hunters, mercenaries, and temple guards. Ideally it's going in, grabbing the stuff, and being back out before they run into anything bad. But there's always something bad. Not only spirits and monsters, but also survivors, be it pleading for help or as strange cults extremely hostile to outsiders.

This seems to provide a good backdrop for three types of adventure: City intrigue, sudden supernatural disaster, and expedition into the weird. All of which can get very dark, but in itself the regular inhabited regions and even the uninhabited stretches of wilderness where the forces of magic are low can be perfectly pleasant places where the characters can make their homes.

What do you think of this setup? Any potential flaws you are seeing or ideas that come popping into your had from reading it?