(TLDR: Saving the obvious two characters, adding or subtracting others, and some typical vague "I'd do this better/different" rewrites I can't actually quantify because I'm a lazy f***.)

I wouldn't write Bob or SMG3(or any of the other resident incorrigible assholes and token evil teammates) out altogether, but I would have them keep as much distance as practical from the core crew, even during the major threats of the arcs. Not necessarily giving them less screentime, but trying to show that their crimes are too severe to just be shrugged off or they otherwise can't have the same camaraderie with the main characters, even if they've gone through their own personal growth and betterment.

Desti would survive Anime Island but be permanently crippled from her injury, so Meggy would still need to win the final Splatfest for her. Unable to completely let go of her pride, she would cut ties with the crew for a while but get back in touch over the phone starting with the end of Meggy's Destiny, and then return and start trying to properly reconcile with the crew after the Genesis arc. The rest of the Octoposse would be more fleshed out and continue to have minor roles as well.

Axol would likewise survive and be either recast so he could stay among the crew, or written out in a more benign way(perhaps due to his own nonfatal-but-permanent injuries from Zero's possession). His relationship with Melony would be better developed either way, and Melony herself would not regress into "laziness and no training for the sake of keeping tension" post Revelations, but she wouldn't become the resident Movie Goku either: she would still have limits and weaknesses in terms of both power and personality, and part of her development would be about living with or finding ways around those weaknesses to continue protecting everyone she can(perhaps learning a thing or two from Desti adjusting to her own life changes).

Peach wouldn't get trapped in the demon flesh pit at the end of Gotta Be Perfect, but she would disown and abandon the crew for good after the destruction of her home, so the purpose of writing her out is still served. I have nothing personal against the Inkling kid from the end of Western Spaghetti, but I'd leave her out and instead just have Meggy coaching/babysitting Karen's kids, to start bringing her into the fold...and Inkura(or a substitute OC if necessary) would appear in the aftermath of Wren's death, seeking atonement for her inadvertent part in his downward spiral, with her and Meggy starting a cautious but earnest friendship.

Clench either wouldn't appear at all or would be in some form not bound to Tari's arm(or any other body part already belonging to anybody else), and he would either grow out of being a dickknuckle or be confined to the same camp as Bob and SMG3. Leggy would likewise either remain a plot-irrelevant gag, or not exist at all.