One possible motive could be that Sakura is brainwashed. Maybe an enemy uses some kind of mind - control jutsu on her and she becomes a puppet to kill Sasuke. Another could be extreme jealousy. If she felt that Sasuke was slipping away from her in some way, in a very dark and twisted version of the story, it could lead to her killing him.
Perhaps in a fanfiction where the world has been corrupted in a different way. For example, if there was a new evil power that forced Sakura to choose between saving the village and Sasuke, and she chose the village at the cost of Sasuke's life. Or it could be due to a misunderstanding. Sasuke could be framed for something really bad, and Sakura, believing he is guilty, kills him in a moment of what she thinks is justice.