It could be an evil wizard. There are many powerful and malevolent wizards in the Fairy Tail universe who might target Natsu for some reason and use dark magic to make him cold.
It's possible that Natsu's coldness is a temporary state. He could be under a spell that makes him seem cold, but deep down his true self is still there. As the story progresses, his friends might try to break the spell and bring back the old Natsu. They could search for a cure or a way to reverse the magic, leading to many adventures and challenges along the way.
Another possibility is that Natsu is turned into a girl by a magic spell gone wrong. As a girl, he discovers new magical abilities or a different way of using his existing fire magic. Maybe the transformation also affects his personality slightly, making him more empathetic and in tune with the feelings of others around him.
Well, perhaps Natsu could be turned into a vampire during a battle with a powerful dark magic user. Then he'd struggle with his newfound vampiric instincts, like the urge to drink blood, while still trying to be true to his friends and his guild.
He could also face challenges within his own guild. Some of the members might tease him, while others might be overly protective. Natsu as a girl would have to navigate through these new social dynamics. Also, his appearance as a girl might attract unwanted attention from some villains who see him as an easier target, but he would prove them wrong with his strength.
In some fanfictions where Natsu becomes END, it often leads to a power - up that is both amazing and terrifying. His physical appearance might change, with more demonic features. His power level could skyrocket, making him one of the most powerful beings in the Fairy Tail universe. He might struggle with the newfound darkness within him, as END represents a very powerful and potentially evil force. This could lead to interesting storylines where his friends in Fairy Tail have to find a way to bring back the Natsu they know while still dealing with the power of END that he now wields.
Maybe Natsu discovers a new magic spell that accidentally turns him into a dragon. He then has to figure out how to reverse it while dealing with the new powers and instincts.
There could be a female dragon named Ignis who is very fiery and passionate, always trying to be the closest to Natsu. Another could be a more gentle dragon named Aqua, who has water - based powers and uses her calm nature to balance out the more intense dragons in the harem.
In addition to Lucy and Erza, there could be other female characters from the series. Maybe some minor characters who have always admired Natsu from afar. For example, that one girl from the guild who always blushes when Natsu is around. Another possibility is a powerful female dragon who sees Natsu's transformation into a Dragon God as a sign of his worthiness. She might join his harem, bringing a different kind of relationship dynamic as she has her own dragon - like qualities and power. And there could be a female mage from a different guild who hears about Natsu's new status and is intrigued, eventually becoming part of his harem.
It could be an old and powerful vampire lord who sees Natsu as a threat to his rule. Since Natsu is a new and different kind of vampire, the lord might want to eliminate him.