1.8-Bo and Lauren's relationship being (temporarily) ruined, especially given that their making love earlier came off as a Crowning Moment of Heartwarming.
2.12 - Masks: The look on Bo's face when Lauren and Nadia are kissing after Bo freed Nadia from her curse.
2.19 - Truth and Consequences. The ultimate wham episode. Trick and Bo telling Kenzi she should leave, Kenzi breaking up with Nate to protect him, Nadia's death...all of it.
Bo draining the unwilling killer Fae in "Adventures in FAEbysitting.
"Delinquents": Lauren finally breaking down over how horrible her life has become, and then breaking up with Bo.
Tamsin pouring her heart out to Bo in "Hail, Hale." Many a fan became a Valkubus shipper after that.
A variation, but Aoife in the season 4 premier. She seems so much healthier, happier, and even younger with her memories altered. Which makes her reverting all the more tragic.
4.11-Hale's death. Then Kenzi's desperate sobbing and attempt to get Bo to revive him.And screaming that she had wanted to say yes to his proposal. Considering the Crowning Moment of Heartwarming between them just moments before this makes it all the more tragic.