Ryuko and Mako's fight in episode 7, especially when Mako realizes Ryuko isn't hitting back and becomes distraught by how close she came to killing her best friend. This is topped off with her thoroughly chewing out her entire family, herself included, for just gleefully letting the fight happen, all with the most miserable expression on her face. To see the premiere source of lighthearted comedy in the series brought down to such lows is heart-wrenching.
And then there is Ryuko's side of the equation. A girl who never had any family life have finally found a family that took her in and treated her as daughter. And then they just cast her away in exchange for happiness and luxury. She was fighting for their sake and all she got in return was betrayal.
Mako risking life and limb to reverse Ryuko's Heroic RROD.
While it's mostly built through flashbacks, Ryuko's situation as a whole. Her mother is said to have died not long after she was born and she had a rather bumpy relationship with her father. Before she was even 10 years old she was shipped off to boarding school and didn't see her father again until the moment he died, not even having a chance to make up with him. No friends, her family all dead... Ryuko is a pretty sad and tragic heroine.
Ryuko's whole life in general until recently has been this when you take a moment to look at it. Always the girl who's always just inches away from reaching anything, only for life to turn around and knock her down a peg or two. Be it the answers she seeks, or even a friend to cling onto... Hell, it's heavily implied that, before Mako and Senketsu came into her life, Ryuko was deliberately alienated by her other classmates for some reason after her father had left her in the school's hands and pushed her to the point where she decided to delve into the bad and ended up becoming a full-time delinquent before the series, presumably just to getsomethingout of her peers besides abuse. And it probably went as well as you'd expect, it's no wonder why Ryuko is always so angry and aggressive as she is with just... howbrokenshe is.
With The Reveals of Episode 18, Ryuko's life has actually somehow managed to become even worse now that we know that she was used as a test subject when she was only a BABY for horrible experiments, then coldly discarded BY HER OWN MOTHER when she was deemed a failure.
As of Episode 16, there's a new angle to look at Ryuko and her father's frosty relationship: After defecting from Ragyo and founding Nudist Beach, Isshin knew his life would be in constant danger and didn't want Ryuko to be caught in the crossfire, at least not until Kamui Senketsu was completed, which is why he sent her off to boarding school. And sure enough, had Ryuko stayed at home instead, she would've definitely been killed by Nui. Isshin deliberately "abandoned" his daughter so she could be safe. And with Episode 18's reveal who Ryuko's mother really is, it's no wonder why Isshin kept her away.
When Episode 19 revealed that Isshin was Soichiro Kiryuin all along, it makes it harder that Satsuki and Ryuko are both avenging his death without realizing that they're sisters.
Ragyo Kiryuin, possibly the worst mother of all time in anime, and one of the worst in the history of television. She only allows her progeny to live in order to aid in her plans, which range from sick and twisted to incredibly sick and twisted and beyond. The thought that someone could and would do such things to their own children without remorse is both heartbreaking as it is Nightmare Fuel.
Look closely during Ragyo's No-Holds-Barred Beatdown of Satsuki in episode 18. You get to see part of it from Satsuki's perspective and for a split second you can see Satsuki feebly raising her hand in defense against her mother. It was already awful, and yet, that little detail makes things so much worse. For a split second Satsuki was not the confident badass that she was portrayed as throughout the series, but a little girl trying to defend herself from her mother's abuse.
Episode 19: Watching Gamagoori, for all of his sheer size and brute strength, fail to rescue Mako from COVERS. He's pinned down and forced to watch Mako be absorbed, and all he could do is scream her name.
Sukuyo's attempts at consoling Senketsu, who's desperately worried about Ryuko's well-being.
Ryuko is not taking the revelation that she's part Life Fiber very well, to say the least.
After a month of waiting anxiously, Senketsu is overjoyed to see Ryuko awake and recovered, but the feeling isn't mutual. She turns on him with revulsion and calls them both monsters; she makes it quite clear she never intends to wear him again. His look of horror and betrayal is heartbreaking, and it's made worse when you remember they had such a seemingly unbreakable bond together.
Satsuki is in terrible shape after being captured by her mother. She has spent the last month being tortured and sexually abused while listening to Ragyo laugh at how pathetic her rebellion was. Then Ragyo basically says that the only reason Satsuki is alive is to be a power source for some sort of giant Kamui. But Satsuki does plan on showing how bad an idea it was to leave her alive.
After spending all that time watching Ryuko interact with Senketsu, it is really sad to see Sanageyama transform and then almost immediately have his Goku Uniform fall apart due to overuse and lack of maintenance.
As if the above wasn't bad enough,after Sanageyama is defeated he refuses to give up, only for his former friends to sacrifice themselves so he and the others can escape. His defeated look and voice, as well as his brief conversation with Gamagoori, is just sad.
The defiance of Sanageyama's old friends from his middle school gang really hurt watching. Especially seeing the COVERS swallowing them up while the struggle, even when they were assimilated in.
Episode 20: Not even one of Mako's speeches is enough to snap Ryuko out of her Heroic BSOD.
That look of shock on Mako's face when Ryuko says that she isn't the Ryuko she knew. Mako got hit as hard as Senketsu.
What makes it even worse is that you can clearly see that, even as she says this, you can clearly tell that it's tearing Ryuko up inside. She doesn't want to leave them, but she feels she has no choice because she's no longer human.
The whole damn scene everybody is trying to console her but are only met with vitriolic insults. Worse, Ryuko is clearly anguished about this whole situation and seems to just not know what do to.
By the end, tears are pouring down Ryuko's face. She looks utterly agonized by whatever Ragyo's doing to her, and by the visions of a happy childhood she could have had with a loving parent who didn't cast her away.
What's even worse is the fact that despite the Mind Rape, despite the tears, Ryuko.Is.Smiling. Ragyo broke her so badly in those few seconds that Ryuko is now happy at what has happened to her.
And all the above scenes in this episode are only made sadder by the song that plays during them, "I Want to Know".
Mako's motivational speeches continue to fail horribly... up to and including Mako literally entering Ryuko's mind to get her to stop wearing Junketsu. You can tell that Mako was trying hard, because there wasn't even any of thatmusic in the background, and yet it still fails, with Senektsu taking a strike meant for Mako and the screen fading to blood-red, leaving the viewer to question what just happened or even if Ryuko can be saved. Thankfully, they're both okay, with Ryuko pulling off Junketsu and losing a ridiculous enough amount of blood to rival Steamboat Geyser, proclaiming that she has to get Junketsu off, or she can never wear Senketsu again.
Ryuko took out her sword and threatened to kill Mako if she got in the way of her happiness. Even if it was fake, Ryuko really did wish to have a normal life and be a normal girl.
The look of horror and betrayal on Mako's face as she is nearly cut down by Ryuko. Had Senketsu not tanked that hit with perfect timing...
Not to mention Ryuko's BSOD when she thinks she's murdered Mako. She is absolutely devastated when she made the strike as Mako makes the aforementioned expression WHILE her High-Pressure Blood is spraying all over Ryuko. Thank god it was Senketsu who took the hit.
Satsuki's fight with Ryuko. Satsuki's forced to fight her brainwashed sister, and she's completely outclassed as well, desperately surviving while she enacts her plan to bring Ryuko back to her senses.
The notion that Ryuko was so devastated at having almost killed Mako, that she rips off Junketsu, a dress whose Life Fibers were stitched to every inch of her skin and body. When she tears it off, she's entirely red and blood is raining down everywhere. She openly screams how she's in excruciating pain but the real tear jerker is that she says she DESERVES IT for how she's been treating her loved ones while brainwashed.
Nui and Rei's situation at the very end of the penultimate episode is very disheartening.
Rei gets absorbed by Ragyo to complete Shinra Koketsu in Satsuki's place, and simply stands by and resigns to it, making you realize just why she was so unconcerned by Nui's threats in the previous episode...she knew full well that she was going to be sacrificed.
Nui has regained a good deal of her composure but still very clearly traumatized from the loss of her arms. Then Ragyo creates Life Fiber prosthetics for her, but explicitly says she only did it so that Nui will be more effective in battle, and does it in a way that mirrors her predation of Satsuki and Ryuko and Nui is visibly discomfited◊ by her actions. Then Nui laments how her new arms don't give her the dexterity she used to have, but that they will do for this last task she has been assigned by Ragyo.
Gamagoori having seemingly died protecting Mako from Nui. Every ally present reacts strongly to it and Mako is the most emotionally wrecked she's ever been, her eye holes literally turn into high pressure water gushers.
Episode 24: Senketsu's fate. After absorbing Shinra Koketsu, he can't withstand its extreme energy and starts to dissolve. However, using the last of his strength, Senketsu shields Ryuko from planetary re-entry, with some parting words:
Senketsu: The time comes when a girl outgrows her sailor uniform. From now on, wear whatever you want. Clothing far cuter than I could ever be.
Ryuko's reaction when Senketsu disintegrates. She gasps, all background music stops, and the most heart-rending scream you've ever heard is torn out of the poor girl's throat.
The final stab in the heart comes in the epilogue, when Ryuko sees a little girl wearing a sailor uniform in the same colors as Senketsu.
After the final battle, Ryuko offers forgiveness to Ragyo, telling Ragyo to come back down with her just like mother and daughter. Think of it this way: Ryuko, despite all the horrible things her mother had done, was willing to give her mother a second chance, a chance at starting life anew and redeeming herself. That takes a heart of 24-carat gold. Ragyo refuses the opportunity and just kills herself instead.