When Barry flat-out rejects the tempting prospect of saving his mother, he explains she's going to die no matter what, be it from illness or accident or old age. All that he would gain from screwing history is more time with her, and it will never be enough so he has to let her go. Even if he's tearing over it.
Malcolm Merlyn's relationship with Oliver takes a turn for the tragic with The Reveal that in this timeline, Oliver was the byproduct of Moira's affair, meaning Malcolm utterly ruined his son's life. He would like nothing more than tell the truth, but the Queens rightfully forbade him to do so. And don't forget his subtle fear when Oliver decides he wants to help rehabilitating the Glades — the same project Malcom's beloved wife wanted to accomplish, and it led to her death.
Since he was Spared by the Adaptation, poor Tommy has to live with the fact that his father engineered a mass-murder in the name of revenge. Even more so as his friendship with Oliver and Laurel eventually ends and learning about the death of Isabel, not knowing she was stringing him along.
Similarly, as badass as it is that Tommy of all people manages to kill Talia al Ghul, it's still tragic that Malcolm continues to manipulate him to do whatever he wants (even if only by telling the truth) and that there's no way Tommy will be able to walk away from this.
Black Siren's interactions with Earth-1's Quentin, Dinah Lance, Sara and Oliver. She's constantly reminding herself they're not her loved ones, but at the same they are her parents, her sister, her boyfriend and she just misses them, she just wants a bit more time with them, just that once.
Jay Garrick's fate at Zoom's hands; since Zoom didn't figure out the Flash's secret identity for a long time, he captured Jay instead: