OK, several interesting thoughts here.
Regarding mutants: I am surprised that I am in the minority in finding Gamma World mutants to be sort of stupid. For me, I guess, what I sort of have in mind is to not have mutants running around doing comic book mutant things (like lasers from the eyes, shapeshfting and so forth). This is not to say that I want a biologist to pick the thing up and say Yes! This is possible! Just that, insofar as I think that having mutants is an intrigue part of any post-apocalypse game I want to have them, and I would at least like a vague tip of the hat to plausibility.
One of the biggest issues, I think, that I had in Gamma World (besides the fact that I found most of the mutations themselves so silly that I was unable to suspend disbelief) is that for the most part the mutants had such a huge advantage over the pure strain humans that for the most part that is all that anyone wanted to play, and it felt unbalanced.
So, what I am thinking is to perhaps model some of the mutations after Shadowrun cyberware (things like stat boosts, and so forth), but to also have some edge/flaw system that must balance (perhaps you have, say, 10 edge/flaw points and can “spend” 5 for edges during character creation but have to take 5 points worth of flaws).
In looking at the back-story of “how did the world get this way”, I have a few thoughts. I kind of want to avoid straight out nukes, for the most part because I don’t really want to hassle with making up radiation rules. To be sure, you can do some hand waving around the issue because “things got lost and forgotten in the breakdown” but I am thinking something along the lines of a global economic collapse with all of the looting and civil unrest and regional isolationism that would be associated followed by some massive global epidemic.
The place that I want to get to with the world is that it is massively depopulated, there are small agrarian communities that are scrabbling to get by, scavengers that that glean what they can from the ruins of cites, raiders that prey on both (and may have set up little feudal militia type holds) and so forth. Oh yeah, and mutants.
I don’t know, off of the top of my head, necessarily what this will offer that others don’t. I think at this stage I am more doing this for fun, and to see if it takes on a life of its own that I am looking for a marketing plan.