I've recently been taken by an idea that won't let me go, which is to run a D&D campaign as if it were a Superhero setting like the Marvel and DC Comics extended Universes.
The idea is to run D&D mostly by the book, but the conceit of the setting is that NPCs (unless they achieve super-villain status) are capped at 3rd level. The PCs are among the elite few who are Big God-damn Heroes. The campaign starts with everyone at 10th level, and they have reached these heights of power by D&Dified comic book logic. Maybe their soul was merged with the soul of a dragon, or they are the child of a God (like Hercules and Achilles), or they pulled an Artifact-level sword from a stone. Whatever. The point is that by one means or another the PCs have been plucked from among the ranks of the commoners to stand with the Super-Heroes
True magic items would be rare. Since NPCs are capped at 3rd level, they won't be making much beyond low-level scrolls and potions. Every significant magic item was either made by a Super-Hero or a mystical being of great power (dragon, angel, demon, djinn, etc.). But the PCs (unless it is part of their character concept) would not be using magic items often. (And when they need one, finding it is a Quest with a capital Q) Instead the normal DMG guidance for when to give items to PCs is followed, but instead of an item the PC develops a new power intrinsic to their existence. A super-power, if you will. The PC doesn't have a Flametongue +2, but instead all weapons wielded by the PC are +2 and an burst into flame if he or she wills it to be.
This is both good and bad for the PCs. It's reliable (you can't lose your power as easily as you can lose an item), but also inflexible. There's no easy way to switch items if the beasty you're fighting is resistant or (worse) immune to what you've got.
Enemies would be straight out of the comics books, D&Dified. Super-villains intent on taking over the golden city, dragons conspiring with evil princes to have the best pick of the virgin sacrifices, hordes of demons trying to break into the realm of men, etc. For the most part, common, everyday life among the commoners would be fairly low-magic, but for the PCs they exist in a rarefied atmosphere of magic and mayhem.