I can understand some interconectedness being appealing, and everyone likes crossovers, but at some point the world gets too crowded (think Kingdom Come) and sometimes the basic themes of the the stories just don't work with eachother. In this case, the whole mutant vs. non-mutants just doesn't work in a world with tons of other superpowered people that no one has a problem with. I just don't buy "person X with magic is a terrible person becaue she's a mutant" but "person Y with magic powers is ok because she isn't a mutant". In the case where the mutants are obviously different in appearance from normal humans, I can understand that there is some prejudice but other than that, normal people would just as easily react with "I hope I'm a mutant and get cool powers" or "I hope some fancy alien doesn't pick me to get unlimited power" as they are with the reverse.

One of the best moves DC did was seperate Vertigo from the mainstream DC universe. Sure, there were some bleedovers, but the worlds immediately felt less crowded and could develop in their own ways without contradicting the established canon. Think how many times someone like John Constantine saved the world (ok, far less than the Justice League, but still). How often wouldn't it have made sense if someone like Dr. Fate had stepped in and fixed things instead of JC? There's a limit to how many times "Oh, Superman was busy saving a falling plane" works as an excuse.