The main antagonist could be the Devil himself. He might see Harry as an intruder in his domain and try to keep him there forever. He could set up all kinds of traps and challenges for Harry to overcome.
Perhaps the main antagonist is a corrupted version of Harry himself. When Harry enters Hell, his own dark side is amplified and it takes on a life of its own. This dark Harry tries to prevent the real Harry from leaving Hell as it wants to stay and rule over the dark realm.
It could be a powerful dark wizard who has made Hell his lair. This wizard might have a vendetta against Harry and wants to use the opportunity of Harry being in Hell to finish him off once and for all. He might control the dark forces and creatures in Hell to stop Harry from escaping.
Another possibility is that an evil wizard from the past, who was previously defeated, gets resurrected or empowered by Harry's time - traveling interference. This wizard could then become the main antagonist, using Harry's actions to their advantage and wreaking havoc on the wizarding world.
One possible plot could be that Harry is sent to Hell due to a powerful dark magic spell gone wrong. In Hell, he has to face his worst fears and demons, both literal and metaphorical. He might encounter lost souls who tell him secrets about the magical world. Eventually, he manages to find a way back, using his wits and some unexpected magical abilities he discovers during his ordeal.
It could be a dark wizard that was previously unknown. Maybe this wizard has a grudge against Harry's family for some long - forgotten reason and is using a very subtle and complex plan to harm Harry. And Fred discovers this wizard's plot when he goes back in time.
It could be a new dark wizard that we haven't seen in the original series. This wizard might be jealous of Harry's fame and power and wants to eliminate him by making him disappear.
A jealous classmate could be the main antagonist. This person might be envious of Harry's popularity or the strange things that seem to always work out for him. They could start spreading rumors or trying to trip him up in his studies.
There might be a character who is secretly from the wizarding world but has turned to the dark side. This character could be after Harry in the Ouran setting, trying to use the chaos of the new environment to their advantage to get to Harry without being noticed by the Hogwarts professors.
It could be Zeref. If Natsu goes back in time, Zeref might have different plans or be in a more powerful position at that time. He could be the main obstacle for Natsu to overcome, especially if Natsu is trying to change things related to the dark magic that Zeref wields.
Perhaps an ancient martial arts master who has gone astray. He might envy Kenichi's pure heart for martial arts and tries to corrupt him. This antagonist could use his deep knowledge of ancient martial arts against Kenichi, creating intense battles between them. Also, he might try to use Kenichi to gain more power in his own time period.
It could be a powerful sorcerer from the time she travels back to. This sorcerer might sense that Elena doesn't belong in that time and wants to stop her from interfering with his plans. Maybe he has some dark magic he wants to use to take over the kingdom or town she's in.
It could be Danzo. In the original story, Danzo was a major factor in the Uchiha massacre. If Itachi goes back in time, Danzo would likely still be plotting against the Uchiha. His thirst for power and his extreme methods would put him at odds with Itachi's new attempts to save the clan.