A mutated Highbreed could be the main antagonist. This Highbreed was accidentally exposed to some other alien energy source that made it extremely powerful and insane. It views Ben's new Highbreed form as a rival and wants to prove that it is the superior Highbreed. It starts attacking planets and Ben has to stop it while still getting used to his own transformation.
It could be an evil Highbreed scientist. This scientist might be obsessed with creating a new breed of Highbreeds that combines the power of the Omnitrix with their own genetic superiority. He sees Ben as the perfect test subject for his experiments and will stop at nothing to achieve his goals.
Maybe a rogue Highbreed warlord. This warlord has his own plans for galactic domination and sees Ben's transformation into a Highbreed as a threat to his plans. He tries to either kill Ben or use him for his own purposes. The warlord could have a powerful army and advanced technology at his disposal.