My go-to game for super heroes is Mutants and Masterminds.
We're at third edition now, with the first edition based on the D20 rules system and each version refining the game.
Because it is skills light (there are just not that many skills), I do not think it is a great choice for sci-fi games, without powers.
But it's really good for supers.
HERO System can do a pretty good job with most genres (it's very flexible) and is fairly straight-forward in play. It just can require some significant preparation before the campaign/session, sometimes on the players' side as well as the GM. It's one of my favorite "toolkit" systems; you can use it to model anything, with a reasonable degree of success, from as coarse to as fine in detail as you wish.
GURPS is a bit less flexible with system mechanics (IMO), but has an extremely robust support line covering various genres and specific settings from comic books/movies/novels/TV.
For non-super sci-fi, TSR's old Alternity system (one of the last things they published) is actually pretty decent. It even has a couple thinly developed campaign settings in Dark*Matter (modern/near future, X-Files inspired) and Star*Drive (interstellar far future, shades of a darker Star Frontiers).
Shadowrun is very good for cyberpunk; take out the dwarfs, elves, orks, and trolls, as well as magic, and you can run it in "pure" sci fi mode.
I've heard some good things about Savage Worlds, but don't have any personal experience with the system.
For Sci-Fi, my go-to system is Alternity. Of course, I had the forethought to buy multiple copies of all the books when the line was canceled, they are kinda hard to get now.
There are actually 3 settings for it: Star*Drive (Sci-Fi Space Ophera), Dark Matter (Modern X-Files/Torchwood style) and Gamma World (Post Apoc. Fallout Style).
There is even a fan made Fantasy rules available online. The strength of alternity, is that the system is flexible and modular. Once you master the system, it is really easy to tweak it to do anything you want (with the exception, ironically, of High Magic Fantasy lol.)
I find Mutants & Masterminds to be a slightly more rules lite version of Hero System. 2nd edition will be very familiar to anyone with experience with D20 products. I have run a couple non-Supers one shots with it. It is very cinematic, so if you are looking for gritty realism, G.U.R.P.S. is your better bet.
Champions/HERO system has always been my go-to system for superheroes.
I have played supers in GURPS, and it works pretty well. The big thing GURPS lacks compared to HERO System is the concept of speed factor: that creatures with unearthly reaction speed can act more often in a round than mere mortals.
However, for non-supers modern-day or scifi games, GURPS has been my go-to system since the 1990s.
FATE (either Core or Accelerated) is another option: It can work in whatever setting you want, and it allows you to define aspects of your character and the setting as you see fit. However, FATE is a rules-light narrative-style RPG system, and that's probably not what you're looking for.
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You have never seen hero system LOL
You have never seen hero system LOLI've played plenty of Hero System. It's not that I'm surprised M&M is liter, I just find it weird that something can be simultaneously described as a "version of Hero System" and "familiar to anyone with experience with D20 products". Hero is nothing like D20.
It's more like the character generation of M&M is like Hero lite. It is a point-buy based power system. You are given a predetermined number of points from which you can buy your stats, feats, skills, and powers. Similar to Hero System, but without the logarithms.
Check out Base Raiders.