I‘m gonna assume you’re talking about DC comics in which case my advice is pick a canon. DC has a bunch of different universes. I’m not a comic geek but I think I can recall a couple of years ago they killed off all the alternate universes and consolidated it into the single New 52 universe (I think they might have also done something similar in the 80s not sure). You also have the option of writing your own canon which may require more work on your part.
I'm failry deep into writing a marvel fanfic. My advice is to keep the story very narrow. I choose not to do that even though i knew it eould go haywire.
Such large universes tend to go very out of wack very quickly.
Depends on the vibe your going for. You could pick a bunch of new or old comics and dance around them. If your going for something more original. You could write about the MC being one of the last remaining members of an extra dimensional race who finds refuge on Earth after their hiding place between Universes is attacked by a mysterious being.