The Mellifer's state after Nick had to Save the Villain. It is made even worse because she doesn't understand what Nick is doing.
Juliette breaking down as she cleans up the house after Nick is attacked in "Game Ogre". She's The Stoic until the cop who drove her home leaves and then cries as she clears away broken glass and other debris. It's clearly hitting her how close Nick came to death.
Lena being captured and turning old. Her daughter and Charlotte will live and lived the same thing, unless something is done.
Possibly even more tragic is the extremes they're forced to undertake to avoid that fate. You can see how much Lena hates what she's doing, but she's biologically compelled to it.
Angelina's reaction to her brother Hap's death. This is what solidifies her as an Ensemble Dark Horse.
Rosalee's reaction to her brother's assault. She is so resilient, but you can still see that she is on the verge of breaking down.
The mouse serial killer. The whole episode is basically you feeling horrified, but wishing for him to have a happy ending. Everything is just so close from getting better, even though everyone knows that it won't. When Martin bursts into tears after being cornered by Nick, saying that his abusive dad is everywhere. Even though he killed several people including said dad, attacked a man in a restaurant, and kidnapped his friend, you can't help but want to give him a big hug.
The bird lady victim of Domestic Abuse. She is just so shy, so fragile and so resigned. She doesn't even want money.
Adalind's home and the scene in it, with her mom, plus way Renard treats her after she becomes human, give her an Alas, Poor Villain vibe of desperately wanting love that she only receives in a callous and conditional way.
Nick and Juliette's meeting at the trailer. It becomes clear that Juliette just won't try to understand, because she won't ever trust him.
Season Two:
Juliette and Nick's deteriorating relationship.
Angelina and Monroe's reunion and the sacrifices she makes for him.
The terrified parents and the kidnapped children in la Llorona, but, also, the Llorona herself. "¡Mis hijos!"
Rosalee having to sit through dinner with her estranged mother and sister.
Her mother isn't that bad, but her sister DeEtta keeps on pushing Rosalee's buttons—blaming her for having to move in with their mother after their father died, and going on and on about how Rosalee was too busy partying up the coast and doing drugs to bother coming to the funeral. Rosalee finally snaps and tells them that she was in jail and had lost everything, and by the time she got out and found out about her father's death the rest of the family had stopped talking to her. No wonder she storms out in tears after.
Apparently Rosalee just can't catch a break right now. Monroe proposes, which should just be the happiest thing ever (and it is for like a minute) but then we meet his parents, and it turns out they're horrible bigots that believe in species purity and get on their case about being in a mixed relationship. She walks out in tears with that one too. If that wasn't bad enough, Monroe decides that he's willing to completely sever his relationship with his parents because of Rosalee. Even though it's the most painful thing he's ever done and he's about two seconds away from tears.
Happily, the two end up getting married, and that should be the end of it, right? Nope. The two are faced with vandalism (including a burning brand in their front lawn), and poor Rosalie has the horrific incident of finding a dead fox on her doorstep, with a phone call warning her that unless she leaves Monroe, it'll be her blood next.
Monroe's mother's reaction to Nick. She and her husband had been in the middle of an argument with their son, and then a Grimm shows up at their doorstep. When Monroe breaks up the ensuing brawl and explains that Nick is his friend, she is almost in tears when she asks "You've hunted with a Grimm?" She really believes for a while that her son has completely betrayed the Wesen world and turned his back on the two of them.
As of "Mommy Dearest", being Wu is pain. Hank by proxy too, since after all he could've been sent to the loony bin if he wasn't tough enough. He's eventually let into the loop, and promptly has a Heroic BSoD, getting drunk, starting a fight and then getting thrown in jail. Bonus points for the Background Music being Delta Spirit's "From Now On", which includes the lyrics "I had a vision about this very thing. But it's probably in my head."
No matter how one feels about Adalind, her reaction to her baby being taken from her is brutally hard to watch.
Juliette believing that Nick has cheated on her. Worse is the way he appears to have cheated; in their bed, with her negligée, not even bothering to clean up after as if he doesn't care if she knows. She's clearly struggling not to cry, holding it together for Monroe and Rosalee's sake but unable to act normal or fathom why Nick would suddenly treat her like that. Then they figure out what really happened, which is actually worse.
Season Four:
Trubel tells Nick that she's leaving with Joshua to help him take his life back. Nick accepts it and gives them Aunt Marie's old truck. The whole scene has a very "leaving the nest" feel to it.
The fate of the Chupacabra. He is actually a coyotyl infected with a disease that turns him into a bloodthirsty (literally) killer. There's a cure, but he has infected his wife inadvertently, and Rosalee only has enough ingredients in her shop for one dose. The husband grabs the syringe and plunges it into his wife's back, ensuring her survival and his ultimate demise. Her grief-stricken Big "NO!" is heartbreaking.
In Death Do Us Part, a woman asks how she was supposed to tell anyone about the fact that her husband's murder was Wesen related without getting thrown into a psych ward. There's a brief cut to Wu, who is visibly shaken - his face tightens and he swallows hard. It's a beautiful moment for Reggie Lee - you can see all the pain Wu went through without him having to say a word.
In Maréchaussée Juliette comes to the realization after being attacked and threatened with death in her home — again — that she'll never be safe with Nick unless she can protect herself. Leading her to conclude that she has no choice but to embrace being a hexenbiest.
Poor, poor Bella Turner's situation in "Heartbreaker." As a Folterseele, her skin secretes a powerful toxin when in the presence of someone aroused by them, which happens more often when it should, because her kinds human forms are always beautiful. This trait led to Bella's mother and her grandmother being raped. To make things much worse, the Folterseele remedy their curse by having their faces mutilated with a branding iron.
Monroe experiencing PTSD from being the Wesenrein's captive. Doubles as a Heartwarming Moment when Rosalee consoles him.
"Mishipeshu" has several tearjerker moments. First, the idea that a young Simon was forced to watch as his father was killed in front of him, then Hank later experiencing what he went through via a vision, which results in him getting possessed. Only adding to it, the third killer gets away scot-free because Simon could be the one getting punished if the case were to be taken to court. Despite this, however, the Mishipeshu posses Deputy Ferris, the officer investigating the case with Nick and Hank, and returns to kill him.
Nick becoming increasingly desperate to help Juliette, only to later find out that she's in police custody and is facing assault charges. Then she basically tells him that she thoroughly enjoys being a Hexenbiest, and then there's this final exchange:
Nick: I'm not letting you out. It's safer for you here.
Juliette: And safer for you.
The gang finding the trailer after Juliette torched it in the Cold Open of "You Don't Know Jack." Nick, Hank, and Wu's flashbacks of the times spent there, and Monroe's worry over the elephant gun (the one he used to kill Oleg Stark) is absolutely heart wrenching.
Few tearjerker moments can top the final scene in "Headache", when Nick finds his mother's severed head inside a box. His reaction is nothing short of heartbreaking. And the nail is driven even further into the coffin when Diana, now a toddler, simply asks "where's my mommy?"
Nick can't bring himself to kill Juliette...so Trubel does it for him.
Season Five:
In "Lost Boys," a group of Wesen kids kidnapped Rosalee, because they wanted a mother. She then learns that despite they are messed up, they are also completely ignorant of their nature and how to live in the world. In the end they are taken back in the system- where they are recruited into the Wesen Freedom Group, as Child Soldiers.
A particularly tragic example of this is when Lily, the only girl in the group, reveals that she's a Fuschbau as well; not knowing anything about wesen, seeing Rosalee woge causes Lily to assume that Rosalee is her actual mother, and is clearly devastated at the "betrayal".
In "Wesen Nacht", Trubel breaks down in tears, lamenting how she keeps bringing trouble to Nick's life. Cue Nick giving her a hug.
The Fuilcré father in Star-Crossed whose son has fallen in with Black Claw. The man tries to talk his son out of it and gets beaten for his troubles while his son stands there and watches; after Monroe intervenes, the son turns his back on his father and goes back to the rest of the Black Claw recruits.
In "Map of the Seven Knights", we meet Monroe's German uncle. The old guy is eccentric and a bit stubborn, but Monroe clearly adores him. He gets killed by Black Claw members looking for the ancient Grimm books he had. Monroe is obviously crushed, barely holding back tears, his only comfort being that his uncle put up a good fight.
At the end of "Taming of the Wu", Nick comes home to see that Adalind has left with Kelley, and a note that states Adalind loves him, and does this protect him.
Meisner's death. That his former ally, Renard, was the one who landed the killing blow, and Trubel began sobbing over his corpse only makes it worse.
Season Six:
In "The Son Also Rises," Eve is hospitalized after being choked into unconsciousness by a creature's hand in a mirror. Nick stays in her room the whole time, and is visibly tearing up as he recalls Aunt Marie warning him that getting Juliette involved with Wesen would be dangerous for her, as well as Juliette's "death" at the hands of Trubel.
"Blood Magic" has a creature that euthanizes Wesen suffering from dementia. The tearjerker comes at the end of the episode when a woman is being attacked by her demented husband. You can see how difficult the decision is for her as she tearfully sits her husband down to be euthanized and tells him she loves him, and in his final moments, her husband remembers her enough to call her by her name.
"I had a vision about this very thing. But it's probably in my head."