The final childhood scene reminiscence between Shiori and the protagonist in Tabidachi no Uta. Dear god, seeing the poor little Shiori sad and all alone with her present for the protagonist, who refused it in embarassement due to the other kids' Girls Have Cooties stance, is absolutely heartwrenching.
Likewise, in the same game and same route, the childhood scene appearing during the symbolic marathon, where the protagonist, in their childhood, couldn't keep his promise of finishing the race and giving to Shiori at the finishing line the headband she entrusted him as a charm, due to an injury. Seeing them both crying out of sadness and frustration is just as heartwrenching, and gives the player further determination to mash those buttons to keep the protagonist running during this Greatest Second Chance.
The famous "Yubikiri shita janai!!" ("What about our Pinky Swear promise!!") scene in Nijiiro no Seishun, especially in the Original Drama Soundtrack, where Sachiko Sugawara's performance is even more heartwrenching. But in either case, Saki's cry from the heart is extremely palpable, and you can't help but feel horrible.
The scene in Irodori no Love Song, where Suzune is no longer able to hold out her sadness at seeing her love for the protagonist unnoticed by him, culminating with an Armor-Piercing Slap. Seeing her in such an emotional turmoil, you can't help but hate both the protagonist for his obliviousness, and the game's developpers for not offering a Suzune Route possibility to the players!
Tokimeki Memorial 2
The anime scene concluding the Childhood Mode, big time. As the protagonist is moving away from Hibikino, young Hikari tries to runs after him, ultimately can't catch up, trips, and starts crying at the loss of her beloved one. Oh boy, is that one absolutely heartwrenching to see.
Kotoko's "Big Reconciliation" Event. After a messy quarrel between her and the protagonist when he instinctively rushed to the hospital after getting news of her having suffered an accident from a panicked Bakuretsuzan, leaving out a date with Hikari, which Kotoko, as The Matchmaker between him and Hikari, didn't approve at all, she avoided him for a whole month, part out of resentment, part out of pride and shyness of reconcilating with him. No longer able to hold out her feelings after that, she isolates herself in the Tea Club Room, and breaks in tears. The sight of that prideful and strong girl cracking down like that is poignant.
Kaedeko's Last Fireworks Festival event. The poor girl, in tears, tries so hard to tell the protagonist she loves so much about her and her family moving to Hokkaido the next day, and ultimately can't.
Kaori's "Farewell" Event, where she suddenly tries to break ties with the protagonist, fearing to trust in him and consequently be hurt by him. The brutality of the Event, coupled with the heartwrenching variation of the game's Leitmotif played in the background, makes the scene powerful. Similarly, when she isn't enough in love in you, and quits school at the beginning of the school year out of depression. Made even more painful if you try to phone Kaori after getting the news of her resignation from Takumi: you'll only get an automatic answer telling the phone number doesn't exist anymore, meaning she has moved away, and cementing the fact she's now lost.
Tokimeki Memorial 3
Yukiko's storyline has one of the most poignant Tear Jearkers in the entire franchise. In this storyline, you get to know the owner of the Candy Shop, an old lady Yukiko adores. This old lady will fall ill during the course of the game, and you will see, together with a worried Yukiko, her health degrading until she dies. Later in the story, Yukiko will discover a letter the old lady left for Yukiko and the protagonist; they read it together, and will discover through it the sad story of the old lady and the man she loved, who got separated by the war in which he died. As such, the old lady exhorts Yukiko and the protagonist to fully live their romance while they can, in the final lines of the letter. Yukiko is very moved after reading the letter, and it shows.
Izumi's storyline is also heavy Tear Jerker-wise. Years before, she lost her childhood friend and lover in a bus accident after coming back from a date at a ski resort (an accident in which she also suffered injuries that require regular surgeries even by the time of the game's proper), and still lives in the memories of him. It's bad to the point that in a late-game Event, where she and the protagonist go for a date at the Cinema and they watch a film with a storyline similar to her Backstory, she's so traumatized, the protagonist will need to take her out of the cinema.