If any game deserves a mention, but missed the top 4 because I have neglected it for a very long time, it is the Hero System, otherwise known as Champions.
A meagre offering, but enough to bring back those halcyon days of number crunching and fist of dice gaming. My friend Mark was the true advocate, my interest was only in playing and I must admit to being put off too much by the up front math, that so many others in our circle were better at milking (more of a writer than a mathematician). Shame, because it is actually quite easy and worth the effort. The Hero System book had I think one more power than Champions and a little cleaning up, making it the “smart” buy, but the Big Blue Book was iconic (at least I have the GM screen). I even re-discovered my uncut flats.
Hero system/Champions 4e is the one. The second and third editions were where I started, but 4e became the main stay and rightly so, before the massive, over written 5e and more streamlined 6e, then the cut to the bone Champions Complete (still 6e) have both come and gone from my collection, but 4e (only the basic Hero System book, not unfortunately the “Big Blue Book”) has been kept.
It has some mild issues, but most agree, 4e was the pinnacle of the Hero systems path, especially in universe development and support materiel. After this edition, like so many games in the early 2000’s (GURPS and D & D also comes to mind), it grew to monstrous proportions, but lost much of it’s character and clarity (perspective).
This game is one of the few that really can stand on it’s own two feet. The system is solid, character generation immensely flexible and comprehensive and the feel, a little bit old school and generous.
Once you have made a character (an afternoons work with a super hero, twenty minutes for a basic human), the game runs smoothly and comprehensively.
If you want to seriously commit to a single system, able to link any genre seamlessly, then this can do it as well as any, especially if high powered characters are the norm. As a bonus it also only uses d6 and has a 3d6 bell curve task resolution.