1. Torchwood. Owen really isn't very nice to Tosh, and for (utterly understandable reasons) he's at his worst in A Day in the Death. Owen's entire rant to Tosh in his apartment is heartbreaking and cruel, the end is the worst: "Maybe that's what you want. Maybe you want somebody who's as screwed up as you. Who's twisted and screwed up like you are. Well, you want to see broken? Do you want to see broken, Tosh?" And he starts breaking his fingers.
2. Buffy. So many intense relationships, but as Buffy/Spike shipper I'm going to go with a small moment that usually gets overlooked. In Once More With Feeling, Spike sings to Buffy to stay away from him if he doesn't return her feelings. Then he shows up at the Magic Box trying to be helpful. Buffy reasonably asks why the change of attitude. Unfortunately, she mentions Spike's song in front of her friends, which leads to teasing from Xander and curiosity from Anya.
Spike says to Buffy: "Fine. I hope you dance till you burn. You and the little bit."
Buffy's wordless dead-eyed response breaks my heart. It's a cruel thing to say - not only to wish death on Buffy, but on Dawn. After all, in Villains, right after Spike tried to rape her, Buffy still trusted him with Dawn. Spike's "I hope you dance till you burn" is even harsher given that Spike likely didn't give one thought to what he had said afterward. To him, it was impulsive, he didn't mean it, whatever. But Buffy had done absolutely nothing to deserve this verbal attack, and I can't believe she wasn't hurt by it.
Fandom has a tendency to assume that Buffy understood how much Spike loved her. That's the basis for a lot of arguments that she had more power in S6. But I think it's more complicated than that. In Wrecked, Buffy is suspicious that Spike slept with her because he was interested in "doing a slayer". Buffy is aware that Spike has some kind of romantic obsession with her, but she seems to change her mind a lot about what that actually means. Given how changeable Spike is - ranging from tying her up and threatening her to enduring torture to protect her sister, giving her speeches about how much he thinks about saving her to telling her she hopes she and Dawn die because her friends were a little rude to him to stopping her from dancing herself to death with a speech about how she needs to stay alive to telling her she belongs "in the shadows... with me"...it's not surprising that Buffy's confused.
3. Supernatural. "If I didn't you know... I would wanna hunt you. And so would other hunters." I have two interpretations of this line. The nicer interpretation: Dean is saying, "If I didn't know you and have a full understanding of the situation and reason to give you the benefit of the doubt, I would go with my training and upbringing and try to kill you."
The less nice interpretation: "If I was able to look at things objectively and not be biased by my love for you, I would kill you."
I think Dean meant something closer to the nicer interpretation. However, given the way he delivers the line, the obvious harshness, I think he left the second interpretation there intentionally. He's lashing out at Sam, and he's trying to scare Sam straight. And for Sam - well, I'm sure he heard the less nice interpretation.
For me, the second interpretation is one of the worst things you could say to someone. It's essentially telling someone you love that they have no worth outside of your love for them. It's cruel. Especially when coming from a family member, since there's always a question with family members: Do they love you for you, or just because of the familial relationship? And, as Dean is well aware, Sam doesn't have many connections outside of his family.
4. Jessica Jones. "I was wrong, you are a piece of shit." Not blaming Luke for a legitimate grievance, but ow. He made her feel like she might be lovable, and then this.