I personally like the gender play in Venture Bros. There's never been a cheap laugh at trans* people and all but Hunter are in fact not trans*.
for a good two or three seasons the joke with Doctor Girlfriend is that she has a super deep and raspy voice. This leads other characters to think she is a man, though not all think is as Dr. Venture is insanely attracted to her. And every time someone says something about her being a man either her husband The Monarch, or a past lover Phantom Limb, reassure us that she is 100% (cis)woman. Later at Sgt. Hatred's house party it's revealed that she has been a long time heavy smoker and has what Sgt. Hatred calls a "three pack a day voice".
I would argue that Hunter Gathers is some type of trans* because multiple times he says he wishes he had been born with breasts, and that he misses the one's he had. But still there's no "tr****y" jokes just bitter resentment between himself and the strip club's bartender, or jokes about "the things he's done for those hundreds". If he is in fact the trans* character he no mere caricature. The fact that he wishes he was born a woman or at least had breasts, is just a part of his character. He can't live his whole life like that since his job is more important to him. It's a nice added complexity to one of my favorite characters.
In the new season they was more antics. as you say Sgt.Hatred starts to grow breasts of his own. This however is a reaction of the super soldier serum he was given in the army and the experimental anti-pedophile narcotics he is on so he stops "touching little boys". But he is still a man, having breasts doesn't suddenly cause him to be some feminine parody. He is conflicted and distraught describing himself as a freak but still a man, he even admits that he some times looks at his breasts and pretends they're a lady's and masturbates; which is totally what a hetero-cis man would do. Also there are a few episodes where one of the titular Venture Bros. (Hank Venture) wears a ladies robo strength suit. He adopts some more feminine mannerisms mostly in the way he sits and the stereotypical feminine hand gestures. But the allure of the suit is that it makes him super strong and that's why he refuses to take it off. if you watch the show you'll know that Hank want's to be a superhero (Batman) and is kind of an idiot. He would let a woman's strength suit change him like that.
Venture Bros. is a great show and I've never found any bit of it offensive, they handle touchy subjects quite well where anything that could be construed as offensive is really a fault of the characters being dumb or ignorant and they are more the butt of the joke than anything else.
yeah... I really like the Venture Bros.
