Maybe it's an old, forgotten evil force that has been awakened. It could be a powerful spirit or an ancient curse that has a mind of its own. Harry has to face it alone as no one else believes in its existence at first. He has to figure out how to defeat it using only the knowledge he has and his own determination.
It could be a new dark wizard who is more powerful and cunning than Voldemort. This wizard might have been in hiding all this time, biding his time to take over the wizarding world. With Harry being alone, he would pose a great threat as Harry doesn't have his friends to support him in this fight.
The main antagonist could be a corrupted part of the wizarding society itself. For instance, a group within the Ministry of Magic that wants to establish a dictatorship. They see Harry as a threat to their plans and isolate him from his friends so that they can easily deal with him. Harry has to fight against this powerful and well - organized group all by himself.