Re: I can't wrap my head around a....
Just like you mentioned Hermit; for me its aliens. I've always liked to run my superhero worlds with as much "realism" as possible, trying to ground the characters in the real world as much as possible. Maybe I lean towards what some have called a "people with powers' sort of game. I've used the approach in both my own superhero world for previous games and in my current game where I use my own modified version of the Marvel Ultimate Universe.
I can deal with genetic mutations and "science gone wrong" origins. Hey, those two are almost like real science. LOL
I can also deal with high tech gadgets and armor. Although, Bloodstone has a good point so I limit the kinds of tech I allow and try to play out the consequences when possible. Even more similar to real science.
When it comes to aliens (and to a slightly lesser extent magic) I just think they ruin the "real" world feel. No invading alien fleets, exiled alien princes, or stuff like that for my world. Or, if there just has to be such things I like to keep them subtle and in the realm of government cover-ups and conspiracy.
DISCLAIMER - This is just my opinion so if you love aliens you just go right ahead and have them in your game. Have fun.