One possible plot could be that Lily is under some dark magic influence which makes her turn against Harry. Maybe a powerful dark wizard has corrupted her mind, leading her to believe that Harry is a threat to the wizarding world that needs to be eliminated.
It could also be that a time - travel gone wrong scenario is at play. Lily from a different time period, where things have gone horribly awry, encounters Harry and, due to the chaos of the time - travel and altered events, she ends up killing him. This could be a very complex and convoluted plot with many different factors contributing to her actions.
One possible plot could be that Harry gains Lily's memories gradually. As he gets these memories, he starts to understand his mother in a much deeper way. He might learn about her childhood, her time at Hogwarts, and how she developed her magical skills. This new knowledge could also help him in his fight against Voldemort, as he might discover secrets that Lily knew.
One possible plot could be that the portraits of James and Lily are somehow damaged or fading, and Harry has to find a way to restore them. He goes on a quest to find ancient spells or magical artifacts that can help.
One possible plot could be that through some magical time - traveling anomaly, Harry ends up in a different time where he meets Lily before she is with James. They might bond over shared values and a sense of adventure, leading to their marriage. Another plot could involve an alternate universe where the normal relationships are disrupted, and Harry and Lily are brought together by fate to face a great evil together, and in the process, fall in love and marry.
One possible plot could be that Castiel is under some sort of dark spell or mind control that makes him turn on Dean. Maybe a powerful demon has manipulated him, leading to a tragic confrontation between the two friends.
One possible plot could be that Harry has been pushed to the edge by the extreme Pureblood ideology which has led to much harm and discrimination. In his quest to end the cycle of bigotry, he targets those Purebloods who are actively involved in dark magic and oppressing others.
One interesting plot could be that Harry meets Lily in a time - traveling scenario. He gets to have a conversation with his mother, learning things about his family that he never knew before.
Another possibility is that an ancient and evil magical artifact is the real antagonist. It has the power to influence Lily's thoughts and actions, and it compels her to kill Harry in order to fulfill some dark prophecy or purpose related to the artifact's power.
In some fanfics, it could be due to a threat she believes she can't protect Harry from. Maybe she thinks that by leaving him, the dark forces won't target him as much.
In such a fanfic, one possible reason could be extreme depression. Maybe he faced overwhelming losses like the death of his closest friends and felt he couldn't go on. Another reason might be that he was under some kind of dark magic influence that made him lose his will to live.
Perhaps in this fanfic, Harry has been influenced by dark magic or some evil entity. This external influence could distort his perception of Lily and turn his normal feelings for her into hatred. Dark magic has the power to corrupt one's mind and change relationships in unexpected ways.