I think part of the villain has to flow from the players too. Not the characters mind you, but the players. Find out what they dislike IRL and what their motivations are. If you have very politically liberal players for example, having a villain who was trod on by the man and now returns to commit acts of anarchy may resonate.
The thing is, your players have to be willing to hear your villain. Not just listen to the guy's rants but really HEAR them. If your players just want to play a game that's just barely not a board game, chances are you're not pulling off a memorable villain.
Finally you as the GM have to have the chops to pull it off. When you're playing the villain you have to make them live and breathe at the table. When dropping in hints and rumors of this villain or inserting the aftermath of the villain's actions such things need to be well delivered.
I've wanted to run a low-level game with a villainess who is nothing more than a CN female human (shapechanger) adept 4. Poor Vanya is just an odd girl, an outsider who lived alone in the woods with her father. She has always envied the girls in town and wanted to be pretty, like them.
Growing up in the woods Vanya spent many nights slipping away to sleep in the moonlight. She heard voices there that calmed her. Her father warned her not to trust the faerie folk but they whispered promises to make her beautiful so she lingered.
Finally when she turned 16 Vanya blossomed. She developed into a pretty young girl and wanted to be among the other girls at the faire that midsummer. She begged her father and he agreed so she made a special dress and sang all the songs the faeries had taught her (adept spells). She and her father went to the faire and Vanya was up with the other girls, coming out to the town now as young women for the first time.
Then the boys pulled the chord. Then Vanya fell under the stage. Then she met the rats.
So Vanya's father took her home. She fell ill with the fever and he went to get a cleric from the town. Vanya wandered into the forest and went to where the voices sang. She begged them to make her better; she pledged anything for her revenge.
Her dark patron rewarded her pleas with a curse. Now poor vanya is a wererat. She has transformed several of the other children into rats with her new powers. She is no mastermind; rather she is a frightened child at once vengeful of her peers and guilty for her actions. Unfortunately her patron has some larger purpose so she must continue plaguing the town.
The PCs then are made aware of Vanya through her father. She hasn't returned home and he just wants his little girl back. There are boys and girls missing throughout the countryside; rats are spreading an epidemic of Filth Fever; the fey have turned spiteful and mean.
This would be a real challenge and I don't think I've got the skill to pull it off. Still, I think it would be really satisfying just to see the look on the players' faces when they get to the final fight where they find a poor teenage girl sobbing "I just wanted to be pretty... to have friends... but they... they TOOK that from me! They stole EVERYTHING! I just wanted it back... I'm so sorry..."