Where do you get your powers from, when you get them?
This is perhaps the greatest question of superpowered world-building. It can influence or even determine politics. It can implicate metaphysics. It can raise grave questions in ethics. It can box in theme. It constrains plot and character.
AND it has to have multiple answers, or else be very loose.
Because if your characters are all the wearers of powersuits from a megacorporation or a crackpot inventor, or all extremely powerful wizards, or all aliens manifesting alien abilities, you aren't writing about superheroes, however powerful the characters are, and however much they fight crime. Despite Iron Man, Doctor Strange, and Superman, you are writing, respectively, mecha, urban fantasy, or science fiction.
All right, maybe superheroes if you hit all the other superhero defining tropes on the head. But probably not.
Much, much better to have a man whose wearing a powersuit, a powerful wizard, an alien manifesting alien abilities, and possibly a housewife who washes vegetables in her kitchen sink and manifests powers when she eats them.
At least, much more in the spirit of the genre.
The downside of this, as Aristotle could tell you, is that this pushes against the story's unity of theme, which is vitally important in making a tale hang together.
The behemoths of superheroes pulled it off by the slow accumulation of such origins over time, but even they found use for something to pull it together: a meta-origin.
I have heard that Stan Lee invented mutants because he didn't want to invent new origins for all of them, but as a technique, some people being born with them is an excellent way to pull things together. So much so that DC invented the metagene as the source of many (not all) superpowered humans in the DC universe.
The trick with the mutation, and the metagene, is that they not only produce superpowers, they produce all kinds of superpowers. Thus they are called a meta-origin.
A gene would not be necessary. For instance, if the super-soldier serum did not produce strength and endurance except when the subject produced that. Perhaps if someone other than Steve Rogers took it, it would produce flight and fire powers. Or weather powers.
Marion Harmond's excellent Wearing the Cape series runs with that. Ever since the Event, people facing high-stress situations (almost always their lives being in danger) sometimes manifest superpowers. Which superpower depend on the situation and the character. A bullet fired at you? You might turn invulnerable, so it bounces off, or intangible, so it passes through. You might teleport away. You might gain superspeed and run away. You might gain the power to turn the bullet to water, or to increase gravity so it falls to the ground.
Or you might die. Origin chasers are an unfortunately common cause of death in the Wearing The Cape world, and your world might need something like that, too, if you want powers to be rare.
(This sort of thing gives a firm foundation to the ever-popular personality powers, where the cheerful, bubbly type has solar powers and the grim, dour soul has snow powers. Consider whether you want that carefully.)
On the whole, I think it helps when some characters do not fit into the metaorigin. Especially if they are mysterious edge cases. This works best, of course, if the character is mysterious himself. It can also be central to the story, unraveling the mystery, but it can just be a way to enlarge the world, and make clear that there is stuff not appearing in the story.
Another way that helps produce complexity is to have more than one meta-origin, though they have to harmonize.
Suppose the Alien Empire is reaching toward Earth. Refugees comes to offer their help. They themselves are aliens and have what would be powers in humans. They also offer their advanced technology, and it turns out that humans can innovate with it to produce powers, though the pilot to use each machine must be carefully suited to it. Furthermore, the Empire uses genetic engineering to produce more useful slaves, and stealing it lets humans produce superheroes.
Or consider a 19th-century steampunk milieu. Inventors whip up steampunk devices and suits. Highly educated classicists study the Greek magical papyri, recently found in Egypt, and learn they contain incantations that turn people into manifestations like a Greek or Egyptian god. Meanwhile, traveling medicine shows peddle their nostrums from their carts, and sometimes, their treatments transform the person who takes them.
Consider your meta-origin carefully.
On one hand, it may just be a plot device that produces powers and thus enables the story. Its nature may be significant in who gets the powers, and how they are distributed, but it should be as simple as possible, to act as backdrop to the story.
Or its nature may be central to the plot. People are born with powers, but can not be discovered before their powers manifest. The plot revolves about the desperate attempt to track down each new superpower, to recruit to your side, before another side gets at them.
Even if the meta-origin does not determine the plot, it may be resonate with the theme. A world of steampunk inventors, classically educated superpowered gentlemen, and takers of carnival nostrums lends itself easily to class conflict of middle class, upper class, and working class.
A meta-origin is both a plot device and a major factor in world-building. Its handling is a matter of great care.
Just found this article and I love it. I always liked origin stories, and it amused me how they've changed over time. (Toxic waste is out of style, now it's all genetic engineering and nanites). In my superhero universe, the fall of Atlantis granted people powers, and the series is drawn more and more back to Atlantis and the catastrophe that sank it. Lots of different power sets that divide into four classes: strength, psi, arcane, or metamorph.
In a sense it seems like almost a historical accident that superheroes became a genre inn and off themselves considering they started as a crossover of different pulp genres.