Cool topic for a thread. I don't know if I can compete with "the Abomination." That is some serious Big Badiness to live up to.
I tend to think, for my setting, along a few different axes. So, the "single worst entity/person" in the setting is dependent on the campaign, the PCs, their choices and development, not to mention flat out level/power. The worst thing in the world a PC is going to encounter at 3rd level is proooobably not the same thing they will find/encounter (release by accident?) at 12th.
I have several really big bad creatures and persons strewn throughout the setting, the histories and mythologies of the setting, extraplanar beings and deities. What is "the worst thing" in the setting? Well, that's kind up to the players/characters, where and how far they are willing to go.
For the OP's present sort of extradimensional "Root of All Evil" kind of thing, I guess that answer is Karos, the Chaosbringer. An "Elder" God [one of the original 10 deities formed to oversee/administrate facets of the Creation of the setting world, and one of 4 that are left/currently exist]. Portfolio includes (Lord of/the First) Evil, originator/creator of Demons, and [the destructive facets of] Fire. Would-be usurper/destroyer of Creation. Something akin to an amalgam of Morgoth, Tiamat [original not D&D], Apophis, and the worst elements of Hades/Loki/Set/Satan rolled into one. Sole purpose/desire is to take over Creation (the material/"mortal" world), burn it to the ground -literally and figuratively "consume" it, and remake it in/for his own image. Karos is [for most "current day" theologies/religions in the setting] the source of all the original evil of the world and "father/maker" of a great many of the existing evil-aligned deities, the demon lords and higher order demons (thus, by extension, all demons), other monsters and mythological source of a great many other woes.
Beneath that sort of "All Evil" godly being there are multiple tiers of villains.
There are the remains of an originally human empire, long forgotten to the majority of the setting's peoples, who sold their souls to a serpent-demon-godling. The mutated "Men of Duus," now known as Gorgons, are a fearsome subterranean society of unknown sciences, magics, and alchemy entirely unknown/lost to the bulk of the setting. Largely serpentine/reptilean in nature they represent nothing of their original humanity: cruel, depraved, alien beyond comprehension to peoples above and below the surface. Their existence is largely unknown to the general populace, though adventurers and other danger-seekers can (and have) crossed paths or heard tales of individual or small patrols/raiding parties of the Gorgon snake-men.
There are the rumors of the ancient lich-lord, Kren Dalek. But his decimated "valley" of evil is lost (or hidden) and whispers of the undead archmage -and his untold magics and endless riches- are now little more than campfire stories.
Kren Dalek is alleged to be in league with, or as mount, or captured/enslaved -depending on the tale- an ancient wyrm of catastrophic power called Yrss Undalig. But it is said the dragon does act independently, every so often, and is attributed -historically- with the destruction of many a fortress and theft of many an ancient magical treasure. Some say the wyrm was even granted possession of one of the Gifts of Doron to serve as its protector and insure it never again saw its way to mortal hands.
Whether there is a legitimate "partnership" between the two, the lich's power is augmented by the legendary dragon (or magics within its treasury), the lich claimed the dragon's hoard and territory for his own, or whatever the true nature of their association is completely unknown/yet to be discovered. But based on the tales of absolute undying power commanded by each, and both, one would have to be a madman to even suggest seeking out either (let alone both) for glory or riches.
For "persons" there is the scheming would-be conqueror/warlord Stelak D'Ensior -wielder of an ancient magic (and evil) sword, leader of a rogue's gallery of maurauding henchmen, and the current (latest) "lord" of the thrice-cursed stronghold (and surrounding realm), Nor Tyrilith, and so holds command over the (substantial) evils and magic contained therein. He is the setting's general -and most powerful/influential- "Skeletor/Mumm'Ra/Modred/Darth Vader."
There are myriad orders and organizations: the psychic-supremacists of the Ruby Shard, the treacherous crime-lords of the Fathen Brotherhood, the assassin cult-guild of Syris (god of shadow and deceit), the cabal of the so-called "Warlocks of Nekri," though I do not use an actual warlock class. The "Warlocks" are a secret intelligence organization stemming from the Magelands of R'Hath seeking wizardly control over all magic (They are deemed magi-supremacist terrorists by most outside realms and publicly disavowed as "anarchists" by the R'Hathi government/ruling class).
There are, naturally, innumerable cults to various demon lords, ancient evil dragons, and other evil deities... and, of course, the disparate agents of the "Temple of Karos." A coherent "church hierarchy" of Chaotic Evil is a somewhat difficult to maintain. So the "temple" is largely independent actors or small cadres -easy to obscure their true natures/intentions, and easy to infiltrate lands to wreak havok and bring about their lord's "rule/remaking" [destruction] of the world. The largely undisputed "head" of the temple is a particularly infamous high-priestess, Dralana the Demonspawn. She has been known to align herself with the schemes of Stelak D'Ensior more than once.
