One time that comes to mind was a few years ago. The party was fighting a vampiric succubus (I was of course being a jackass GM as all GMs should be) and one of the PCs, a halfling rogue named Rhyla, was taken down. The rest of the party felt overwhelmed and retreated, leaving her behind.
So of course Rhyla became a vampire. Who really hated the party for leaving her behind.
When Parisha (the vampiric succubus) ended up ascending to godhood later on, Rhyla became a divinely ranked vampiric halfling rogue with some pretty nasty habits. Like impersonating random mysterious assassins that liked to kill people the party interacted with. Or just about anything else she could get away with that wouldn't make the other gods crack down on her for overly interfering with humanity.
The party was powerful, too, leveling up to almost 20 over the course of several years of real time, and eventually managed to defeat Rhyla in an astonishingly well-planned surprise maneuver. The players were clearly thinking about this in their off-time as when she appeared at a very inopportune moment, they jumped into action, using wishes and miracles and other 9th level spells to open up two gateways to the plane of elemental water while simultaneously force caging her in some obnoxious geometric patterns that held her there just long enough to let that running water do its anti-vampire thing.
It was an epic end to an epic villain and a well-deserved victory. But I think the reason she was a great plot hook is that the party felt responsible for her existence as a villain. After all, they couldn't argue that they left her behind, knowing that a vampire was kneeling over her fallen body.
This last weekend I may have witnessed another birth of such a villain. Only time will tell, but it has some similarities. The party tracked down and defeated a leprechaun.
Yea, yea, but please understand that my leprechauns are fallen gods that are (mostly) forgotten and are really pissed off about it. He was the controlling force behind attacks on a cretin village (small gnome-like sage creatures) who unknowingly had his last surviving holy text on an ancient stone tablet.
Well, the party knew that the leprechaun would just keep reforming as long as this final holy text existed. So all they needed to do was destroy the tablet and rid the world of a dark, ancient god forever.
Here's the problem - along the way, the party found a little girl who was a creation of this dark god - a spiderwere, which is a spider that can change into human form. Most spiderweres have the intelligence of your average house spider, but this girl was special. She was learning to talk and play like a real little girl. The party got attached to her antics and she got attached to them after seeing the werewolf change forms (which she bonded over).
Destroy the god, and the girl dies. She needs him to exist.
So, the party decided something I hadn't anticipated at all. Maybe I should have, but... anyways, they decided not to leave the girl and the text with the cretins, or a safe town, or anything else - they decided to become the caretakers of both. They took the undecipherable dark holy text and the little girl and as far as I can tell have decided to take off from town and put distance between them, and let the leprechaun reform and come after them.
An epic villain in the making, perhaps?
photo credit: sally_monster via photopin cc