Power corruption is a common theme. Just like in many stories where Naruto turns into a villain, it often starts with him getting too much power too quickly and it corrupts his ideals. Another theme is betrayal. For example, if he's betrayed by the village, he might turn to the dark side.
I think Orochimaru could also fit the bill. His experiments on himself and others are really out there. He's constantly looking for ways to gain more power and immortality in some really strange and unethical ways. His snake - like features and his ability to shed his skin like a snake add to his quirkiness. He's not your typical, straightforward villain and has a lot of idiosyncrasies that could be played up in a fanfiction.
Kaguya could be an interesting choice. She is extremely powerful and has a complex backstory. Her motives were initially self - serving and evil. If she were somehow resurrected or a situation where Naruto had to interact with her in a different time - line, it could make for a great fanfiction. Naruto's ideology of peace and friendship could clash and then potentially influence her.
A powerful and corrupted sage could be the villain. He has delved too deep into forbidden arts and mastered hypnosis among other dark techniques. He views Naruto as a potential obstacle to his goal of spreading chaos and Mei as a valuable asset to be controlled. He uses hypnosis to try and manipulate them into doing his bidding. This sage could have a backstory of being shunned by the ninja world for his unethical practices, which has led him to seek revenge and power through any means necessary, including using hypnosis on Naruto and Mei.
The sense of isolation could be a motive. If Naruto never truly felt accepted in Konoha despite his efforts, he might snap. He's always wanted to be recognized, but if that never fully happens, he could turn on the village. For example, if he's constantly passed over for important missions or not given the respect he thinks he deserves as a powerful ninja.
She could be a hero. In fanfiction, a female Naruto might use her determination and unique skills to protect the village. Just like Naruto in the original, she could have a strong will to overcome any obstacle and befriend those who were once enemies. For example, she might form a bond with Sasuke-like characters in a different way, using her charm and understanding to prevent him from going to the dark side.
If Naruto loses all his friends in a tragic way, perhaps in a battle against an overwhelming enemy that the village could have prevented. His grief could turn into hatred towards the shinobi system. He may decide that the existing order is what causes all this pain and destruction, and then he starts to work against it, becoming a villain in the eyes of the village.
It could be Orochimaru. He's always interested in new forms of power and experimentation. He might see Wolverine as an interesting specimen to study and try to extract his healing factor or adamantium for his own purposes. This would put him in direct conflict with both Wolverine and Naruto, who would naturally oppose Orochimaru's evil plans.
It could be a new ice - using ninja who has a grudge against Naruto. Maybe this ninja wants to prove himself as the most powerful ice user and sees Naruto as a threat, so he freezes Naruto in ice.
Danzo could be a great main villain in a Naruto Frankenstein fanfiction. He's always been power - hungry and secretive. He might use the concept of creating a Frankenstein - like being to gain more power for Konoha in his own twisted way, but really it's all about his own control. He could be using parts of dead ninja's abilities or something like that, and Naruto would have to stop him.