Compared with other heroes, the Defenders acquired a particularly unusual rogues' gallery. So when Jennifer Walters landed her own comedic series as The Sensational She-Hulk, she inherited some of the non-team's earliest enemies.
With Chondu the Mystic still upset with the new body he received in Defenders #35, the other members of the Headmen surprised their teammate yet again—this time by attaching his head to a cloned body of She-Hulk from the neck down (Sensational She-Hulk #1-3).
She-Hulk also faced Xemnu the Titan, who resurfaced with a new set of schemes to repopulate his home planet, including an experiment to transmogrify the green heroine into his bride (#11).
Be it comedy or tragedy, in a misbegotten effort to subsume the Defenders brand into the Fifty States Initiative, Iron Man recruited Nighthawk, Colossus, She-Hulk, and Blazing Skull into his own federally-sanctioned vision of the team, headquartered out of New Jersey (Last Defenders #1).
Disappointed by his handpicked heroes after only one mission, Iron Man disassembled this version of the Defenders part-way into the six-issue limited series.
On a deeper level, Iron Man had a hard time coming to terms with the original concept of the Defenders. The non-team had long succeeded in making a home for Jennifer Walter's cousin Bruce Banner in a way the Avengers never could (Incredible Hulk #279).
Yet whatever misgivings Iron Man may have had, he the not have the "last" word on the fate of the Defenders.