As you can probably tell from my vadwyrms and wyrmanoids posts, I see some potential in a worm-focused setting, In addition to being the king of all monsters, purple worms and other giant worm-related creatures lend a more horrific feel; potentially Lovecraftian in scope, but even a more localized giant worm catastrophe. The horror, for me, is that the menace is mindless. There's no bargaining with giant, hungry worms, and if a couple small incursions turn out to be a hint of a worm apocalypse, where cities shall be tumbled and mankind becomes wormfood, there's a more intense feeling of doom than if some villain, like The Sorcerer of Wyrms or the world's smartest worm, is ultimately to blame. Maybe you can't just ward off the apocalypse by killing one guy... maybe you have to save the people you can and find a safe place to rebuild civilization.
You could almost do that with the undead, but because of necromancers and mastermind undead like vampires and liches, you don't really see mindless destruction as a major theme. It's always a LotR-like battle to save the world, with skeleton armies directed to swarm key locations. Haven't heard of anyone doing a campaign like "The dead walk again, but no one's to blame. Or maybe some necromancer caused it all, but he was the first victim."
And there's the additional invertebrate terror factor. Worms have no skeletons. They have no eyes, or shouldn't (some classic purple worm and remhoraz pictures really annoy me because they add eyes.) There's something just a little more horrifying about a faceless maw coming towards you.
That's why I came up with the wyrmanoids, "humanoid" monsters that have no faces and no language. If I were going to put together a worm campaign, the wyrmanoids would not be masterminds, or even a primary focus of the campaign. They are maybe a side effect, and a foreshadowing, and a foil. They would want the worms to eventually consume the surface, but that's not a master plot; they're just crazed cultists, getting in the way, and perhaps drawing attention to the fact that the worm apocalypse is a possibility.
There might be other side elements that fit thematically with a worm apocalypse. Like: normal-sized flesh-eating worms that cause corpses and skeletons to rise as mindless undead. I wouldn't want to overdo this, though. Not everything should be turned into worms. Most of the game, especially at the beginning, would be about other things, standard adventuring things. The worm apocalypse is just something to worry about that gets worse over time.