It depends on what you mean by pretty much everything.
If by everything you mean you’ve changed the setting, ending, and maybe even merged or changed characters, but retained the dynamics…then honestly, I don’t see why anyone would shoot it down?
Legally, it’s different enough to be its own, so…eff 'em, lol
But if by change everything, you mean…change it so that Psycho is now about bears making pies…then fren, that person you pitched it to might just be a telepath, because there’s not way you can see a resemblance between them, lol.
Honestly, sometimes you just have to deal with that as a writer, whether from yourself or others. The only advice I can give is that the passion behind a story can be incredibly transformative, for both the writer and the story.
Don’t let your fear of unoriginality hold you back from creating something. The world would literally be lesser if you didn’t do anything.
Well, how about just your favorite book or movie, or something?
Essentially, the exercise is just to show you that every piece of media is similar to or inspired by other things, but that doesn’t stop them from being different.
I know your question is how do they become different, but that’s actually…pretty difficult to answer because it’s so subjective to every story.
What differentiates similar stories can be anything from the gender of the protagonist, to the setting or era it takes place in, to the genre, or altering the tone or themes.
There’s really no single answer, because it will change depending on the work.