The time travelers who were flung to the "wrong" point in time and spent years living as temporal fish out of water with nobody to relate to. Particularly so in the case of Kiera's partner Elena, who arrived in 1975. Imagine being sent back to the 1970s from 2013, never mind 2077, especially if you're black like Elena. The worst part is that she's suffering from severe Alzheimer's, which was cured in her original time.
Kiera dealing with the loss of her son in "Second Opinion".
Kellog's breakdown when Maddie, his supposed grandmother dies in front of him, especially after the reveal that his sister was killed in a similar manner.
Kiera having her hopes of returning hope destroyed again when she realizes that the time machine Jason built is really just a model version made of old bicycle parts and CO2 tanks.
Sonya's betrayal of Travis: To elaborate, Travis learns from Sonya that their mentor and father figure, Kagame, just performed a suicide bombing, which devastates them both. And that Kagame's present version has just been born in the same hospital where they are. Sonya then pulls a gun on Travis, and explains that Kagame wanted her to succeed him instead of Travis. When he tries to reason with her, she shoots him six times in the chest, and he passes out while silently weeping on the floor. What really sells it is Roger Cross's subtle yet incredibly emotional performance. You can see the culmination of the betrayal of his lover and mentor have on him before he passes out.
Emily dying in Alec Sadler's arms.
In a flashback to 2067, Kiera admits she's joining the military not to protect her family (it was good timing), but because she believes it's the right thing to do. The "crime" she protected them from was owning books.
In the 2070s, you can have debts piled on just for not being sufficiently zealous in saving corporate barons even if it would be dangerous to do so. A mixture of heartwarming and tear-jerker for this in Kiera's case since she saves two children when her boss is more concerned about the financial loss from said wealthy people.
And now one of the Alec Sadlers is a prisoner of the Freelancers, leaving Emily to think he abandoned her.
Sonya has just watched Liber8 effectively cease functioning as a group due to the multiple whammies of learning that at least half its members had secret agendas — most notably, Curtis Chen for the Freelancers — and that their actions at least partly precipitated an even uglier Crapsack World than Kiera's "past" of 2035 with corporate gulag complexes. In short, once more than one person gains the secret of time travel, it is possible for the multiple travelers from multiple timelines to work at cross-purposes in ways which create drastic, unpredictable changes. The "soldiers" in Liber8 are at least able to roll with what has happened, and Lucas is a tech wizard and while time travel seems to hurt his brain, he's cognizant enough of the implications to not waste time grasping at straws. But Sonya's forlorn sense of hope that Liber8 can accomplish what they set out to do is a starkly moving contrast to the rest of the group's utter cynicism.
Travis tries to convince Sonya to move up north with him now that Liber8 is gone, but she still wants to do one more job. She ends up sacrificing herself to kill Dillon, and the scene where Travis finds out doesn't even need words to show how devastated he is.
Kiera accepts that "her" timeline is gone for good, even as she asks the surviving Alec Sadler to build a better future than his other self would have done.
Kiera's CMR creates the (almost believable) illusion that she has returned to 2080 and her son; she is told all the events of the series were just a dream. Alec wakes her up from the false return; her reaction to that is a weary and sad resignation.
The series finale. Kiera's goodbye to Alec and Carlos, followed by her return to the future, her reunion with Alec and seeing her son again... then the Wham Shot in the park and manyWham Lines from Alec. It was basically expected with the way time travel works in this series, but still a massive gut punch.
Alec: You made a better world, Kiera. Kiera: What? Alec: We thought you died that day. Carlos, Julian and I dedicated ourselves to building a better future. And we steered civilization inspired by your sacrifice. Kiera: But Sam? Alec: This is the price for making the world a better place... this Sam will grow up in a world free of violence... Kiera (now seeing another version of herself with Sam): No. Alec: ...free of revolution, free of corruption. His future is bright, and it's because of you Kiera. It's the price of love, real love. You'll understand, in time.
Additionally, Carlos Fonnegra never got to see Kiera again.