How about regions of space where the laws of physics are different from those in normal space? That is, when you enter a system or sector with this property, the game switches to a "patched" set of data files, which would supplant the original files in places where they conflict! So you could have a system where, say, shields are at half strength, or to-hit chances decrease twice as fast with distance, or any combination of weird effects!
If this is implemented, it's only one step away from loading multiple mods at once and resolving the conflicts via some sort of internal diff program!
And if that's too much, there could always be multiple sets of complete data files which apply in the various anomalies or regions of space!