Kiriya's anguished scream of grief over his sister Poisonee's death at the hands of Pretty Cure. Said event leads to...
Kiriya revealing himself as a villain to his best friend Honoka, who he correctly identifies as Cure White and challenging Pretty Cure to a duel in episode 21. Cure Black and Cure White try to reason with him but to no avail. He attacks them and they transform. When he clearly outmatches both, Mipple and Mepple urge them to finish him with the Marble Screw, but the Cures refuse. Instead, they try to bring him to his senses, telling him he could change his ways and be a normal student. Still, Kiriya is not moved, answering that death awaits those who defy the Dark King and continues to fight...until he badly injures Cure White. An anguished Cure Black asks how he could treat someone who wanted to befriend him so cruelly. Finally, Kiriya comes to his senses. He acknowledges the strength of the Cures' bond and hands over his Prism Stone. Heartbreakingly, Ilkubo appears moments afterward to take him to the Dark King and certain death.
Also the end of episode 22. At first glance, it seems like a lighthearted Breather Episode until the ending: Honoka cries until she runs out of tears that night, never really getting over what happened to Kiriya
There is also a pretty good one in episode 42. The goon squad figures out that separating Nagisa and Honoka is actually a smart move. They do so, and proceed to mentally assault them, pointing out their weaknesses and declaring that darkness will prevail, etc. Nagisa and Mepple end up hiding on a subway station to escape for a moment, and wind up playing shiratori to pass the time. Given Mepple's speech pattern all of Nagisa's words have to begin with "po"... or eventually, "ho". No surprise that the only word she can think of is... Honoka. Sniff. Of course, pissing off a superhero is a really bad idea, and watching Nagisa smash through an entire army of Zakenna is awesome.
And topping it off is the scene in the season finale/episode 49 when Mipple and Mepple go to a kind of eternal sleep after using all their power, all while Nagisa and Honoka tearfully beg them not to. At least they wake up again in the next season.
Alas, Poor Villain moment from Kintolesky and Shitataare, both competing for the title strongest warrior of Dark Fall for the entirety of the episode. Facing Spiral Heart Splash head on and losing, Shitataare prepares to bail out. Cue Kintolesky holding her arm and saying that strong warrior will accept defeat from better foes with dignity. And he considers her a strong warrior, essentially a love confession from him. They both succumb to their death looking at each other's eyes.
Westar and Soular being pulled into a Delete Hole. They get better later, but still; Westar being pulled in after protecting Passion and Soular allowing himself to go even after Berry tries to save him and saying he's sorry they couldn't be friends is just wrenching. Passion and Berry screaming their names in despair is the icing on the cake.
The monsters of the week in this series are Desertrians, which are created from characters' negative emotions. They exist to destroy everything in their path while ranting about their problems until they are pacified and defeated by the Precures. Before this happens, however, the characters they are born from tend to go through some pretty heartwrenching ordeals.
Episode 5: A boy is torn between his thoughts that his father cares more about the family noodle shop than his son and his reluctance to disappoint his father. The real Tear Jerker comes when Akira's Desertrian breaks down crying after nearly destroying his father's shop, still conflicted between his two opposing feelings.
Episode 14: Nanami is a Stepford Smiler who must care for her little sister Rumi since their mother passed away, literally locking away her sadness out of the belief that it's the adult thing to do. They manage to make things work until one Mother's Day when Rumi, feeling lonely without a real mother, misinterprets her older sister's cheerfulness to mean that she feels no sadness towards their mother's death and runs away from home. When Nanami tries to stop her, Rumi slaps her and tells her she hates her, and Nanami begins to crack and tells her that she doesn't care about her. Naturally, Nanami immediately regrets this, but before she can set up her smile and make up with Rumi, she gets turned into a Desertrian by Sasorina as Rumi watches in horror. In a Crowning Moment of Heartwarming, once Nanami is saved, she has a dream of her mother comforting her while she's crying before she wakes up with tears in her eyes to find Rumi apologizing to her, and the two promise to smile together.
Episode 16: Azusa, president of the school's theater club, is bossy towards her clubmates when all she really wants is to share her passion for acting with everyone. When she competes with Erika to see whose club is better, she becomes so bossy that her clubmates decide that enough is enough and leave the club all at once after calling her out for being unfair. Azusa dejectedly continues practicing by herself, but what really crushes her is when one of the lines she’s reciting happens to be, "I am all alone."
Although Tsubomi lives happily with her parents, they were rather neglectful workaholics before the start of the series. This was a painfully slow development that began when Tsubomi was very little, with her parents gradually seeing her less and less before going to work over the years until they stopped seeing her altogether. The sad thing is that Tsubomi would continually see them off with a smile regardless of her increasing feelings of loneliness until they become so unbearable that she breaks down crying when she sees a mother bird acting so attentively to her chicks. If her parents hadn't returned briefly to pick up some notes they forgot, they probably never would have even noticed their daughter's pain. Though they manage to repair their relationship, the whole ordeal is implied to be what turned Tsubomi into a Shrinking Violet with low self-esteem in the first place.
Everything relating to Cologne's death. ESPECIALLY the end of episode 34.
Dark Pretty Cure's Final Moments and Death, soon after that is the death of Cure Moonlight's father, and the Crowning Moment of Heartwarming that ensues. To elaborate:
Dark Precure has revealed the reason she wants to Kill and Replace Moonlight/Yuri: to earn the approval of her creator/father-figure, Professor Sabaaku... who was really Professor Tsukikage, Yuri's father, brainwashed by the Big Bad Dune. After an epic final clash, Yuri runs to her now-free father, who confesses that, after all he's done as Dune's brainwashed slave, he no longer has the right to embrace her. Just then, Dark staggers to her feet, limping toward Yuri and her father even as she is slowly dying, screaming for Yuri to get away from him. Professor Tsukikage simply walks over to her and, guilt-ridden, explains how he'd created her partially from Yuri's DNA, to serve as "a soulless puppet" to dispose of Cure Moonlight. He then embraces Dark, telling Yuri that Dark is her younger sister, and then calls Dark his daughter. At this, Dark Precure finally lets go of her anger and hate, calling him "Father" with a tearful smile as she Disappears into Light in his arms, all while the tear-jerking BGM piece "A Tragic Memory" plays.
Less than 10 minutes later, after Dune has curb-stomped the Professor, Yuri, and Tsubomi, the latter two hard enough to knock them out of their transformations, he starts charging up a killing blast. Professor Tsukikage lunges forward and grabs the blast. He turns back to Yuri and tells her to take care of her mother for him, and then the blast consumes him, ripping him to shreds right before his horrified daughter's eyes. As Yuri breaks down, she starts to embrace the rage and hatred that Dune has awoken in her, only for Tsubomi to hold her back, tearfully begging her not to fall into the same darkness that has caused so much suffering already, to stay the "kind and gentle Yuri-san" whom she looks up to. Thankfully, Tsubomi succeeds in pulling Yuri back from the brink, and they & the other two Precures proceed to overwhelm and thrash Dune.
Episode 21. Siren, under the control of the Noise of Evil, is set to sing the Melody of Sorrow and effect the whole town. Cures Melody & Rhythm are in no position to stop her, Mephisto is standing overhead waiting, and Hummy is held captive by a Bind attached to the top of the clock tower. Rather than beg or cry, Hummy simply smiles at Siren and talks about how she'll always be Siren's friend, following up by singing the song she and Siren sang together as children, making Siren remember all the good times they've had together. When she tries to then sing the Melody of Sorrow at Mephisto's order, she just can't do it; all she can do is break down sobbing.
Episode 36. Cure Muse's pleading with Mephisto, her father, to come back to her and be the man he used to be. She decides she can't possibly fight him, because even if he's brainwashed, he's still her beloved father. Then she uses The Power of Love to defeat him/free him from Noise's control...and they two share a tearful hug as Mephisto apologizes and promises this will never happen again.
The ending. Black Hole's stripped the Pretty Cures of their powers and is threatening to take away the Prism Flower. Doing so would separate the Earth from the fairies' home worlds (and thus render the girls powerless). One of them suggests to use the power of the Prism Flower to restore their powers for one last attack, but it would end up doing the same thing. With no other option, the girls go for it. After Black Hole's destroyed, the credits roll and we're greeted by heartbreaking still shots of the girls in tears over their sacrifice, followed by clips of how the fairies met the various teams. After the credits, it leads to a very awesome Heartwarming Moment.
And beforehand, when the fairies explain how to activate that same attack, we're treated with a scene where nearly every fairies, especially the young ones, started bawling on the prospect of separating. Then we're treated with a flashback of a previous scene of an annoyed Hibikitelling Hummy to leave to a place where she'd never come back. Realizing what's gonna happen, Hibiki completely broke down and hugged Hummy, apologizing that she didn't mean what she said and bawls so hard. Few scenes later, we see Kurumi morph back into Milk, just to cry on Karen's hug. You seriously need a lot of tissues ready when seeing this scene and the ending above.