This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Rosario + Vampire
First Season of Manga
Ruby's past. She was just a normal girl who lived a normal life with her family, until everything was taken from her by a drunken human driver.
Tsukune turning into a ghoul is a truly sad moment.
He loses complete control over himself and cannot turn back. Inner Moka sees no other solution but to kill him, but as she moves to fight him Kurumu and girls come in between them, and tell her that they won't forgive her if she kills him, for a moment Tsukune briefly looks like he's back to normal, but then he attacks Kurumu and wounds her. Inner Moka then promptly attacks him, and Kurumu, instead of feeling afraid for her life or being angry at Tsukune, begs other girls to stop Inner Moka from killing him. As Inner Moka continues to beat Tsukune her thoughts and facial expressions clearly show that she is truly sorry for having to kill him, and is filled with guilt for turning him into a monster, finally as she prepares to deal fatal blow to him she yells his name, before she is stopped by Ruby and Headmaster who luckily have a solution for Tsukune condition.
The following Hospital arc, continues were the previous arc ended.
It starts with Tsukune waking up from a nightmare, in which Inner Moka stabs him through the heart and kills him.
As he comes to his senses the exorcist expains his condition, that he will have to wear the Holy Lock unless he wants to be transformed back into a ghoul, then he notices the girls in his room who were waiting for him to awaken, and everyone is present except Moka, whom the other girls prevented from seeing him as they hold her responsible for hurting Tsukune.
Later Moka decides that it would be best for Tsukune for her to disappear from his life, but as she turns to leave Tsukune notices her, and tries to comfort her. But she tells him that she fears hurting him again and for that reason she can no longer be with him.
Mako Yakumaru, an assassin sent to kill Tsukune, injects Moka with special substance that allows Mako to control people. Later, Moka controlled by Mako confronts Tsukune with a scalpel to kill him, who gets cut and falls. As Moka moves to deal the killing blow with a blank look on her face, Tsukune can only desperately ask Moka "why"...
Second Season of Manga
The "Flower Offering" arc has Mizore attempting to seduce Tsukune so she could escape from an arranged marriage only for her plan to fail due Tsukune being Above the Influence.
After that she is kidnapped by the Snow Priestess and brought to her fiance while Tsukune is left to freeze to death in the snow.
And after that she's almost raped by Miyabi, who steals her first kiss and causes her to be Driven to Suicide, only to be rescued by Kurumu in very heartwarming moment.
The death of Marin's husband, who was killed by Kamiya in front of her, with her being powerless to do anything.
Moka's past. And Akasha's sacrifice to save her and Aqua.
Moka being abducted by Fairy Tail. She was forced by Aqua who would otherwise kill all of her friends.
Kurumu accidentally hitting Tsukune with her "succubus charm". She knows it's the wrong thing to do, but can't bring herself to un-charm him. All she wants is to know what it would be like for him to want her, just for a little while, even if it's not real. Even charmed, she can't get him to even say "I like you" to her, and as she tries, she slowly breaks down into tears over the fact that she can't hear him say it. Finally, knowing he won't remember when she breaks the charm, she tearfully tells him "I love you" over and over anyway.
There are hints that Tsukune actually broke her charm spell on his own and was able to see her Anguished Declaration of Love. He just acts dumb afterwards for her sake.
Reading the chapter with that in mind it seems like he was actually free of it directly when he woke up in her room and played along just to cheer her up (he comments on how depressed she seemed when he met her earlier).
It's really apparent in one translation, where among all of the stilted "I like you"s he tells Kurumu, he says only one, clear "I like you" as she's starting to cry.
Ling-Ling's Taking You with Me attack against Aqua Shuzen, and Fang-Fang's reaction to the fact that he's almost about to lose his sister figure. Luckily Touhou Fuhai saves her in time, but he didn't know that was going to happen.
The series really likes to hammer home how much Kurumu suffers from her heartbreak. She's present for when Tsukune confesses to the dreamworld version of Moka, and when he tells her that he needs to get stronger to be able to protect Moka, she runs off in tears. She nearly collapses when she's talking to Gin, because succubi live on love.
Kahlua's almost death in chapter 64. As she dies from the wounds she got from Kokoa she begs her to forgive her and Gyokuro, and asks her to forgive her for not being much of an older sister as Kokoa tearfully tells her that she also loved them all.
Chapter 65-2, it's one of biggest wham chapters ever, if not the biggest. It shows the brutal death of Jasmine who was the only friend Aqua had in past, they were so close that they treated each other like sisters. They lived in a human village where they blended in and lived happy and peacefully despite being poor. Only one day a bunch of humans killed Jasmine because of rumors that she was a vampire. She was tortured then "skewered" and by time Aqua found her she was already partly eaten by crows.
It can be said that Jasmine's death is Aqua's Start of Darkness, which caused her hatred of all humans and fueled her desire to destroy them.
Alucard using his tentacles to injure Tsukune and Moka, stabbing her through the chest and greatly damaging the rosary. And despite being injured himself Tsukune moves to Moka and hugs her, the look on his face saying how broken he is.
And finally, the Floating Garden crashes into the human city, likely killing hundreds of citizens. And the words on the last panel imply that this will lead to war between humans and monsters. Akasha's dream of achieving coexistence has gotten a lot harder.
Fang-Fang's anguish over not being able to protect his friends during the fight with Xilong. He up and acknowledges the fact that he's weak after his first opponent loved reminding him about it, and the miserable look on his face as he says it makes you kind of feel bad for all the crap he's been through in the story.
Chapter 66 keeps the hurting in the feelings coming with Outer Moka dying in Tsukune's arms as both come out and admit their love and feelings for each other and having their first real kiss. (And probably last if her death sticks.)
In the last chapter, Akasha returns, only to sacrifice herself again along with her fellow Dark Lords (this time for good) to stop Alucard once and for all. Right before she dies, she tearfully says farewell to her daughter Moka and to Tsukune, whom she fell in love with as "Outer" Moka.