Gwen was originally supposed to be a classmate and a close friend of Ben's instead of being his cousin.
Cannonbolt was originally meant to be in the original set of 10 aliens, but was eventually dropped in favor of Diamondhead. His early design looked more like an insect and he had two shells in each side of his head, along with knobs which would pop up.
Ghostfreak was a part of the opening but due to his departure he was later replaced with Cannonbolt.
Originally the omnitrix was supposed to allow Ben become alternative versions of himself instead of aliens. This later became the idea for Ben 10 Omniverse which has to do with alternative versions of Ben.
The series was heavily influenced by old Hanna-Barbera action/adventure shows, such as Jonny Quest and Secret Squirrel.