I had a couple ideas. Although none that I've actually used in campaigns.
1.) The Ad-Infinitum Cannon- A device that would siphon conceptual infinity out of the Grand Abyss (the huge literally bottomless pit at the center of the first layer of the Abyss) and focus it into an infinitely powerful energy beam capable of firing between planes and utterly destroying anything that it's aimed at. Basically a combination of Starkiller Base from Star Wars 7 and the Ad-Infinitum Siphons from the game Afterlife. The campaign would focus on the varying factions vying for control of it as its being built and the varying factions trying to stop it from being built; this last category would include various demons who want to stop it due to its potential to end all the fighting.
2.) Proper, movie style zombies that create spawn, carry deadly disease, can take ridiculous amounts of punishment, and sometimes suddenly move fast for a moment instead of their usual slow gait.
3.) A flesh colossus with a sibriex for a head
4.) Tungsten rods dropped from a spelljamming vessel in the upper atmosphere
5.) An SCP-Society-esque cult that steals all the magic stuff and in doing so plunges the world into conditions reminiscent of the real medieval period
6.) A fleet of seven spelljamming ships, each bearing a figurehead in the shape of a dragon, collectively rigged with an apparatus that duplicates the means by which Tiamat stole Krynn from its original crystal sphere.
7.) The Temple of Elemental Evil's bottom floor reimagined as some kind of evil reverse version of the temple from The Fifth Element that is capable of firing a death ray when activated by the correct ritual
I'll post more when I'm less tired and more coherent