If Ryuko took Asuka's place, Shinji would have never got back in the robot.

Ryuko would have taken care of everything & killed anything in front of her path without any emotional trauma & regrets - Like a pirate without a moral compass coming back home after some of those regular raping & pillaging.

Rei would predictably receive curt comments from Ryuko, but they'd actually be good dynamic friends eventually as "protective-Ryuko mode" eventually kicks in from the fact that Rei fills the void that Ryuko has from missing Mako.

Shinji would still have his defeated fetal position scenes, so he'd still be relatable - for me.