A plot idea could be that the sister has amnesia due to a vampire - related incident. Maybe she was bitten by a new type of vampire that causes memory loss. The other characters then have to find a cure while also protecting her from other threats in the vampire world.
You can also explore the impact on the relationships within the Vampire Diaries universe. Maybe the sister was in a relationship before the amnesia. Now, her partner has to deal with her not remembering their love. It could lead to some really interesting plot twists, like the partner having to fall in love with her all over again while she discovers new aspects of herself.
Perhaps the Salvatore sister was turned into a vampire long before her brothers, and she has been in hiding all this time. When she finally reveals herself, she has a whole different set of vampire ethics compared to them. She could teach them new ways of co - existing with humans without causing too much harm, which would lead to a lot of interesting interactions within the Mystic Falls community.
One plot idea could be that the OC sister discovers her vampire siblings have been secretly using her blood for their own gain. This betrayal could lead to her seeking revenge. She might team up with other supernatural beings in Mystic Falls to get back at them.
One plot idea could be that the sister, after being drugged, has some sort of psychic connection with the vampires in The Vampire Diaries world. Maybe she can see their memories or feel their emotions, which leads to a series of adventures where she tries to use this new - found connection to help or hinder the vampires' actions.
Perhaps the sister has a special power that she's not aware of, and the sleeping spell was cast to keep that power dormant. In the fanfiction, a vampire who has a soft spot for the sister might try to wake her up, but in doing so, risks awakening her power which could be either a great asset or a huge danger to the town. They could face challenges like having to deal with the witch who cast the spell in the first place, who doesn't want the power to be unleashed.
One idea could be being reborn as a long - lost relative of the Salvatore brothers. Maybe you have some hidden power that was lost in the family history and now you have to navigate the vampire - filled world of Mystic Falls while trying to figure out your new abilities. Another plot could involve being reborn as a witch in the fanfiction world. You could use your magic to either help or hinder the vampires and other supernatural beings in town. You might also be reborn as a human with a special gift of seeing the future, which would put you in a dangerous position as everyone in the Vampire Diaries world would want to use your power for their own ends.
One idea could be being reborn as a long - lost relative of one of the main characters. For example, a long - lost sister of Elena. This could stir up a whole new dynamic in the Mystic Falls gang. You could bring in new powers or a different perspective on the vampire - werewolf - witch drama.
A common plot element is the mystery surrounding the amnesia. Usually, the 'ofc' (original female character) has no memory of important events, and the vampires in the story are often involved in either causing or trying to reverse it. For example, a vampire might have compelled her to forget something crucial, and the story then unfolds as she tries to piece her past back together.
One idea could be a powerful vampire using mind control to make Elena forget her love for Stefan and fall for him instead. This would create a lot of drama as Stefan tries to figure out what's wrong and win her back.
One idea could be waking up as a new vampire in Mystic Falls. You could explore the confusion and newfound powers. Another could be waking up in the middle of a vampire - hunter conflict, having to quickly choose a side. Maybe you wake up with a strange connection to one of the main characters, like having their memories or a special bond with Damon or Stefan.