GREAT THREAD!!
I love sharing these ideas. They're like miniature story hours!
My all time favorite villain (which I can claim credit for) was an intelligent psychoactive skin. At the beginning of the campaign, my PC's had come across an all-metal ship with no sails (a spelljammer -the first on our world). Toward the end of the session, they managed bring down the walls of force protecting the ship's hold. One of the things they found was a transparent cylinder with ornate caps at either end. Inside swirled a blue and gold liquid of some kind. One of the party's twin dwarves thought it was a special ale and tried in vain to open it. He passed it off to the half-celestial fighter who, upon touching it, heard a faint voice in his mind "That one is unworthy. Free me, brother, and you will have my eternal gratitude."
The PC opened the cylinder easily enough (also of note, there were githzerai runes around the lid warning of the evil inside. but no one on our world speaks githzerai yet.)

The psychoactive skin lashed out and immidiately engulfed the PC. It sunk into his pores, sighing a mental "Thank you...." and was thereafter silent....
That is until the PC was alone much later with one of the dwarves. The half-celestial had been feeling bad vibes since the ordeal. The item's Ego asserted itself, the PC blew his save, and the blue-and-gold skin spewed forth around him. The PC(named Kaelraunt) dropped his bastard sword, grew 12" long claws and proceeded to lay waste to the hapless dwarf. The rampage was on. The skin hunted the party nearly brought them all down before he was beaten. Melting back into Kaelrants's body, the celestial knight attempted to take his own life then and there to avoid such a confrontation again. A battle of wills ensued and the skin swore that he would not attempt to kill them anymore. He devulged that his name was Demensus, and that if Kaelraunt killed himself, even under these circumstances, that they would both be damned.
It was quite an interesting ride after that. Demensus would take over Kaelraunt's dreams and fill them with gruesome replays of the skin's former murderous accolades. Demensus, it seemed, was formerly a mortal known throughout many worlds for his merciless savagery. He had been defeated once, only to be ressurected by priests of a god of murder. Unfortunately for them, he had gained a great deal of power while in the Abyss. He made it known to his host that the githzerai finally managed to capture him and imprison him in the psychoactive skin so that he would not be ressurected again or turned into a demon or worse. The seals that bound him were so strong that only a god could open them, presumably to finally pass judgement on the wretched being. This was Kaelraunt's first clue to his heritage but it would be lost in the sands of sleep.
Despite Demensus' evil, Kaelraunt's valor held firm. Until, during one particularly nasty nightmare, the heavenly knight could take no more. He lashed out at Demensus in a blind rage. It would be his undoing. In the midst of the battle, Demensus switched their souls, placing the knight's into the pyschoactive skin. Demensus woke first, and rid himself of Kaelraunt upon the floor.
Demensus had learned, through Kaelraunt's mind, the truth of their quest: the artifact they were assembling could grant godhood. The PC's would give the item to the one mortal worthy of it, the human king Equitus. Now in Kaelraunt's body, Demensus stole the pieces they had already assembled and made off for the next piece. Kaelraunt was met by Alauraseus, his heavenly brother and told the truth of his heritage: that the knight is in fact a heavenly creation of Optimen (THE god of Good on our world), a child, if you will, of a god. Alauraseus granted Kaelraunt a temporary body which, he said, would not last long.
For several more sessions, the PC's were chasing Demensus across the world, and each time he managed to be one step ahead of them. At last, he grew weary of the cat-and-mouse game. One of the pieces was near a sanctuary for elven nobles. After murdering nearly a hundred elves, the PC's finally squared off against an extremely powerful Demensus who had been
futher enhanced by the many pieces of the artifact. It was a battle royale but in the end Demensus was brought down with the help of two githzerai NPC's (a powerful psion, and his psychic warrior cohort) and a final stand by Kaelraunt, toe-to-toe with his nemesis.
Demensus' essence was sealed into six amulets by the psion. One was given to each PC and the psion kept one (actually, Kaelraunt turned his down, leaving the psion with two. He gave it to his cohort). Near the very end of the campaign, the PC's were in what they believed to be a secure room, held in suspended animation by a powerful priest while their souls searched for the final piece of the artifact in the lower planes. When they awoke, having retrieved it, the priest had been assassinated, their amulets were shattered, but they were unharmed (along with the pieces they had already assmbled).
One can only be left to wonder who the assassin was and if the final two amulets that hold Demensus are still intact....