The Search & Destroy handbook modifies Supers! for action-adventure games. Since I don't have S&D, I can't comment on it. However, I can think about the qualities of a genre or subgenre and whether a particular game meets (or could meet) those needs.
Way back when Champions became The Hero System, I figured that any system that could do superheroes could also be a generic system. With age, though, it seems to me that there are some qualities that make a good superhero game that don't necessarily make a good game for another genre, though changing or bolting on rules or subsystems might do the work.
And there are certain genres where that might be true. But most genres without powers use skills to distinguish the characters, and a system that models superheroes tends to gloss over the skills, making them broad, maybe making them additions to your attributes, so that a character can attempt anything unskilled.
In order to fit in the characters who are super-attributed (super-strong, super-fast, super-smart), the systems also tend to compress the low end. In Supers!, for instance, aptitudes really span from 1-4, and everybody has a 1. In ICONS, the attributes run from 1-6. While that's not much worse that D&D, where the supposed 1-18 scale is really -3 to +3 (the attribute modifiers), it certainly feels more constrained.
What about the settings or genres where the characters have powers? ICONS might be used to make a kick-butt Vampire game, for instance, where your clan represents a set of powers you can choose from, and you all get one of a set of Qualities that reflect your clan and vampiric nature. You would have to bolt on the actual powers, defining them as necessary. You'd lose the blood points mechanism (unless you added it) but you could use the Qualities in the same way.
Supers! makes a nice action-adventure game (theoretically--as I say, I haven't looked at S&D yet).
With the right trappings, either one could be a nice high fantasy game, with races and characters who can eventually get strong enough to lift mountains. Both provide resilient enough characters that you could play something like zero-to-hero without worrying too much that your character will die near the beginning of the campaign. (I probably wouldn't go for straight S&S, though, but on the other hand, I have Jaws of the Six Serpents for that....)
Either of them might do well for some of the less-hard science fiction, too. They'd make great systems for something like Star Wars, though you'd have to figure out a mechanism for the Force. (Actually, the more I learn about Kylo Ren's backstory, the more he sounds like a failed character in a Star Wars game...)
They're both best for comics. One is a little more four-colour than the other, but they're both good. And in the realm of comics, I'd love to see someone do the equivalent of Leaving Megalopolis with them.