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Tear Jerker: W.I.T.C.H.
The early episodes of the animated series that dealt with Elyon abandoning her friends, parents and whole world as a result of brainwashing, especially since it took most of one whole season to resolve, instead of just being a fluke. It's like all those scenes from An American Tail, where Fieval almost finds his parents, all over again. Worst of all are the moments that dealt with Cornelia's relation to Elyon; when they threw out a Rosebud to a character who had up to that point been portrayed as consistently superficial, rude, and obnoxious, and she actually showed deep concerns about wanting to help her friend out of trouble, her teammates rejected her pleas.
"E is for Enemy". When Susan laments to Will about her having sleepover and not asking permission and not feeling sorry about it. The girls have better reasons for it. The viewers know the real reason. But Susan doesn't. She believes that what she is saying is the cold truth, but it isn't. Then, the expressions on the girls' faces when they see Will's expression. You can just tell they won't to say something to Will's mom. Just wanna hug Will and tell her it's going to be alright.
"H is for Hunted". Will creates an Astral Drop of herself to do her laundry while she helps her friends prepare for a party. Astrol Drops are normally unable to feel emotions, but when Nerissa changes Will's Astral Drop into an Altamere, it gains all of Will's emotions and memories, including her attachments to friends and loved ones. Excited about her new life, Altamere Will has fun at the laundromat before eating all the food in the Vandoms' fridge. Her new zest for life immediately extends to Will's mother, who the Altamere sees as her own mother. She happily hugs Ms. Vandom before inviting her to the party at the school. When Will realizes how much trouble the Altamere is causing, she and the other guardians, thinking it's still a normal Astral Drop, begin chasing in down in an attempt to absorb it back into the Heart of Kandrakar. The Altamere, who loves her new life as much as anyone would, reacts violently, and a vicious fight ensues between Will and her. After the Altamere desperately explains to Will that she has feelings and emotions, Will then breaks down in tears, embracing her tightly and promising never to absorb her. However, Nerissa uses the distraction of the emotional display to fire a burst of lightning at Will, and the Altamere sacrifices her life to save her creator. A tearful Will offers to absorb the Altamere into her being, which would allow its experiences and memories to remain intact. The Altamere accepts and fades into Will's body, becoming one with Will's consciousness.
"M for Mercy", where Nerissa invokes the soul of the ex-leaderess of CHYKN, Cassidy the Guardian of Water, to try convince her come back to life through Nerissa's magic. Cassidy has even forgiven Nerissa's murder of her, so she's got no regrets and refuses Nerissa's multiple offers... until Nerissa visits Cassidy's still living mother, Emily. Cassidy going all "... Mom..." when she hears Emily say she still misses Cassidy, only to become Nerissa's brainwashed puppet as soon as she cries and wishes to come back and be with her mom.
"O is for Obedience" for Caleb, When he learns that Nerissa is his mother the look on his face afterwards really says it all.
Just these words: Garbage! Worthless garbage! Like you!
What makes it worse is that Irma only said it out of frustration and the look on her face is enough.
From the comics, the brief fight between Irma and her mother Anna from "Water Shadows" (#25) leads to a mit of an emotional Wham Line. They're yelling at one another, and Anna tells Irma "You don't talk to your mother like that!" Whereupon Irma snaps: "Right! My mother!" The utter look of devastation on Anna's face is heart-wrenching, as is Irma's immediate reaction of guilt and regret — especially since this is how the comic reveals that Anna, despite the resemblance, isn't Irma's biological mother.
The death of Will's pet dormouse. Especially after all she went through with her Jerkass dad.
In issue #82: Energy, Will remembering all her friends. Especially Taranee, which shows a small bit of dialog from issue #1.