I personally have a lot of trouble understanding the belief that Regina has been screwed over the most, for many of the reasons that have already been mentioned here. Obviously it's difficult to measure which character has had it the worst, but no matter which way I look at it, I just don't see how it can be Regina (even though this point of view seems to be pretty common among fans). Say we measure "being screwed over" just in terms of a character losing someone they love, since that's pretty much the worst thing that could happen to anyone. Yes, Regina lost Daniel. But Snow lost both her parents, Emma lost Neal and Graham, Hook lost Liam and Milah, Rumple lost Neal, Charming lost his mom, etc. And let's not even get into the fact that Regina herself was responsible for some of those deaths. Of course, there are other ways that Regina has been "screwed over", like Cora's abuse and Rumple's manipulations. But really, the whole town of Storybrooke was abused by Regina, since she cursed them all and took away their agency. So even though, yes, Regina has definitely had her share of hard times, I don't think it's been worse than that of the average Storybrooke resident.
I know some fans viewed the whole Marian thing (and now the Zelena thing) as Regina being screwed over, but the thing (for me) is that Regina chose to walk away from Robin back in the tavern. She chose revenge and anger over happiness. Plus, since Regina was the one who killed Marian in the original timeline, I had trouble sympathizing with her potentially losing Robin when Marian came back to life. Also, lots of characters have been screwed over in other, arguably worse ways, like Snow and Charming never getting to raise their child.
I totally get that some fans love the character of Regina and that her story resonates more with them, but I really have trouble understanding how anyone can objectively argue that Regina has been screwed over more than the other characters.
ETA: I would love to hear alternative perspectives on this because maybe I'm missing something with Regina. Again, I'm not trying to argue that she hasn't been screwed over, just that she hasn't been screwed over "the most".