From "Blast of Silence", when Wallace Pike shoots himself in the head after the bells and factories start up again. Even more so with the fact that he saved the mayor from his own contraption, but found that suicide was a better alternative to the sound.
Also earlier on after the bomb kills Richard Welsh, his wife Cecily (who had been haughty seconds before) is close to tears as she is remorseful of her behaviour and thanks Murdoch for trying his best as time would have run out anyway.
In the Episode "Artful Detective", Season 8, Episode 18, George is arrested, suspected of murder of Edna's husband who was NOT dead all along, as he was at war. It's understandable why George would have done such a thing. George has had his heart broken many times in the show; Edna is his latest sweetheart. To witness the outcomes of a violent husband on his Edna and her son, it's easy for Murdoch and Co. to suspect him of killing Edna's husband in order to be with Edna and to protect her from her violent husband. It's heartbreaking to see everyone being torn apart from this turn of events.
The death of Lillian Moss. Emily is heart-broken.
The end of "Wild Child". Murdoch and Dr. Ogden give Roland back to his rightful father.
In "The Missing", Watts reveals that his sister has been missing for 15 years, ever since they were both children. A few episodes later, he finds her again, and she tells him that she never wanted to be burdened with the task of raising a child, and left because she wanted to.
"Up from Ashes": The revelation that Jackson didn't survive the ambush.
"Brother's Keeper". Watching the quirky, affable, and seemingly detached Watts break down upon learning that his foster brother was dead over the course of Murdoch's investigation into Watt's purported shooting of a suspect is heartbreaking.note When the foster brother's body is discovered, Murdoch confronts Watts with the theory that Watts discovered the killing, and murdered the killer himself in cold blood. Watts didn't know until then his brother was dead, and thought he was the killer and was trying to take the fall to protect him.
The truth behind the killing in "Forever Young" is a tragic one. The victim, a young woman who had been dying from tuberculosis, is revealed to have been accidentally killed by her father as a result of a desperate attempt to cure her. Inspired by a realization that the radiation from sunlight kills viruses and not fully understanding the nature of the then-recently discovered X-Ray, he subjected his daughter to prolonged X-Ray exposure, unwittingly killing her. In his grief, he kept her body in a glass coffin, much like Sleeping Beauty, until he died from a heart attack a decade later, at which point his widow (under the advice of an Amoral Attorney) hatched a plot to plant her body and fake her murder, with the intent of marketing the X-Ray device as an Immortality Inducer by showing how the machine had kept her from aging for a decade before she was "murdered". Even worse, the widow and attorney get away nearly scot-free for their actions; while the intent to defraud thousands of people was there, due to the way the law is written, the fact that money had not yet changed hands means that no crime was committed, there's no hard evidence that the pair knew the machine was the cause of the woman's death so they can't be convicted for knowingly endangering the public, and while they can charge the attorney for the desecration of her corpse for his role in their scheme, the maximum sentence is a mere 12 months while they can't prove that the widow played any part in it, meaning she gets to go free.
"Prodigal Father" features a case of Bipolar Disorder that doesn't shy away from how badly it can hinder the life of someone suffering from it, and if not treated, everyone around them. The man in question is a businessman with grand ambitions, an uncanny knack for foreseeing highly successful ventures decades before they eventually end up happening, and an talent for successfully pitching his ideas to investors. Unfortunately, most of his ventures crash and burn when the depression part of his Bipolar Disorder kicks in and leaves him borderline catatonic for the duration, causing the venture to fall through and losing the invested money. The killing in the episode was, in reality, one part of a husband-wife team trying to kill him accidentally drinking a poisoned drink intended for the businessman as part of a revenge plot for costing them their considerable fortune on a previous investment. When Murdoch and the rest of the constabulary (including George, who learned that the man was his long-lost father, and Brackenreid, who had invested a large amount of his own funds and the constabulary's Widows and Orphans Fund into his latest business) learn of his former ventures, they initially believe that he's a conman, when in reality he's merely a man with the best intentions held back by a debilitating mental illness nearly half a century before it was fully understood.