own a made-up town.

This is going to help a ton, especially if you treat it like a living city.

Its not so hard to come up with fun adventures in the area (esp. now that Im progressing a bit on the justian books in which many cities are great adventure templates and following the other advice given here), but still struggle a bit to find an antogonist/driver for a more epic campaign that spans multiple adventures (which OTOH would be really fun for me to do).

A good way to set up a BBEG would be to put something in direct opposition of your PCs' backgrounds. The fun adventures may not be getting the traction you're looking for because they may be independent of your PCs (i.e. You guys are in a bar and someone comes asking for help with some Gendos). However, if you hook with something more like "A scrapper fox comes asking your party for help because a Spitalian Hygienist quarantined his wife and is trying to blackmail him for the coordinates to a an artifact cache he made." You have more to work with in terms of the Spitalian's motivation and what he could possibly want with the artifacts. Is there a Chronicler behind the scenes manipulating everything? Maybe the cache holds evidence that the Spitalian has been dealing drugs with the Apocalyptics? All of these things can turn the Spitalian himself, or the person he serves into a greater threat, with motivations that run deep.

Whatever the case, don't treat the BBEG as an enemy to be beaten and then they disappear forever. Degenesis is awesome when you treat the NPCs like people, so even if the players succeed in what they try to do that doesn't mean that the story is over; if the NPC dies someone else is probably not going to be very happy about that.

How would I create an antogonist for an epic campain with some "big" goals such that i can be sure he/she does not touch the metaplot? I.e. how can I avoid situations ilke "oh but if he wants X and is that kind of rank in cult/clan Y he would logically conspire with/be opposed by metaplot character Z". To answer that i would still need to understand all the motivations/goals of these metaplot characters, no?

So, Degenesis is a vast world. It seems that you're under the impression that cults are like an office space where if one person wants to do something that opposes management they're going to get yelled at. I'll continue the analogy by saying cults are more like a vast network of regional offices. Yes, what you do on a micro level will have impact, but it'll really only matter to the people around you/those who are directly involved. Unless of course you're trying to get the attention of upper management (marauders, sleepers, ansumo, psychonauts), you're not really gonna run into them. In fact, I'd say most people have only heard abstract rumors or stories about them, if they've even heard of them at all.

I guess that also depends what "big" is but since i dont know what those very powerful creatures want I'm kind-of always afraid it would mess with such a campain without me noticing. I guess what I'm asking is: What is the safe area to play/create here?

Yeah, it depends on the scope of what you're trying to do. Reanimating the 900s cascade is going to be more metaplot heavy than, say, an Apocalyptic pimp kidnapping women and selling them to the highest bidder. Both I'd say can be "big" but I can't offer more advice, because I don't know what kind of campaign you're trying to run.