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Misato is a lost little girl in a grown-up's body, and that makes the age difference a little less inappropriate, a little less weird and creepy.
And I don't think any kind of relationships among the characters we see could ever be anything but weird and creepy anyway.
Because Eva isn't about giant robots. It's about damaged people trying to take comfort together on the eve of Armageddon. Every relationship it shows is dysfunctional and broken, every single one.