I've actually run this very game a couple of times (once quite successfully, two other attempts crashed and burned). It hits me right where I live and sits right at the intersecting points of all the things I love to deal with as a GM.
So. I'm making a tentative offer to see if I can I make this work. However, I can't meet you on all your requirements.
Little Wrinkle:
Maximum of four players. And I'd be leaning toward three. When I play a real-life immersion game I don't kid around. And if I'm managing marital dynamics and inter-familial tensions and job politics, it works best with a small group.
Big Wrinkle:
System. This is a big one. I can't do any of the systems you mention. Either I don't know them well enough or dislike them. So if we're gonna do this thing, this is where we have to start.
Here's what I can do:
- Classic MSH. It's free and fun and simple enough, but it's going to offer power-levels probably grander in scope than we're looking for and it's really lousy for modelling anything on the 'normal' scale.
- White Wolf/oWoD. It's a bit of a Kludge, but it's easy and intuitive, it's good for dealing normal people and handling social assets and conflicts, and between all the various game systems, there's enough material to come up with rules for powers
- Something else. We could use one of the free rules-lite systems. The Window, Risus, or Fudge. Or something similar. Heroes Unlimited maybe (heh)?
Everything else you mention (gritty-real, street-level powers, transhuman, immesion in real life problems, world's first/only supers, GM-directed sandbox, meta-plot), I'm all over all of that.
Let me know if you'd like to proceed.