Story of OW's life: they could have done this "UwU I'm so spwecial" Tumblr bullshit better.
Theoretically, Echo could have been the game's first 'non-binary' hero. Non-binary in the old fun way (i.e. make a good character and have the Tumblr specials project whatever bullshit they want onto it, but never, ever create a character for the sole purpose of fellating the fucks). If only because the entire core of her character identity is "copy this, copy that." Having a sentient machine lack a sense of self due to its programming and entire purpose, hindered further by her creator being dead and thus leading her to have no nurturing, guidance, or assistance that isn't entirely for the benefit of whoever wants to use Echo that day, could have been interesting. When she cocoons, she even looks like those 'eggs' these circles love breaking so much, it's perfect! It would also help fill in the holes of her character design and story dissonance connection, though that would likely also require re-working her existing kit. Maybe throw a shielding ability her way to replace her melt beam, allow her wobbly bombs to also heal nearby allies upon a kill, and bam.
Venture, if they weren't dumb fucks, should have just been MtF. "Yep, here's a short king who went female, isn't science in our future wonderful? All you special gender babies get everything you could ever need! It's a real scientifically chopped woman! Huzzah!" However, as mentioned above, it's not actually about the medical and mental turmoil of constantly feeling like you're in the wrong body for these people and alleviating the negative effects of a mental defect: it's about appearances, plain and simple.
Regardless, in this reality, the Venture shit is stupid. She's a girl with shitty teeth and a qUiRkY personality who let herself go and feels terrible because there are more fuckable chubby nerd women in the future (Mei) and out of a line up of every character in OW, people would pick Roadhog's slab o' bacon over her weird punch-able face any day. She's the perfect self-insert of some of the most insufferable fuckers on the planet, portrayed in a good light because self-reflection doesn't exist, and I hate her for it. From a kit perspective, she's fine, ig? I've barely played her.
Disclaimer: Humoured the non-binary/trans thing for the sake of the post, I do not think Venture should actually be trans at all.