The few times where girls have looked or acted visibly extremely uncomfortable around me, or act creeped out, that's what hurts.

Disregard them.

I mean this in the most humble way I can possibly say this, but I'm a guy who checks a lot of women's "boxes" for what they're supposed to want in a guy; I'm traditionally good-looking, work in a good job while finishing my final year of an advanced degree, am fit, am well-groomed, dress well, yada-yada. Point being, I'm about the furthest thing from "creepy" that one could imagine. Currently single, so I sometimes talk to women I meet, either with them approaching me or me approaching them.

About 50% of the time, we'll trade numbers. Around 40-45% of the time, I will get a polite rejection, the typical "I have a boyfriend" or what not. However, once out of every 15 or so girls I talk to, I will get some batshit crazy reaction.

Something along the lines of:

\ - "Why are you talking to me?! I, like, don't even know you!" (as if I don't talk to people get to know them first)

It's not like I'm approaching these women randomly on the street either, it's usually at a party or at the library or something similar. Nothing I do invites a reaction like this. I've consulted friends who've witnessed me approach girls and all have confirmed that there's nothing creepy about what I'm doing.

The solution is to disregard those girls. I honestly believe they're immature or actively take pleasure in rejecting guys. There's nothing you can do to stop or change them, so don't even worry about them.