This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Hyperbole and a Half
Adventures in Depression offers a very realistic portrayal of depression and the self-loathing that comes with it. Many of the scenes are still funny, but in a brutally depressing manner. "Oh, you're going into the kitchen? Cool. Go fuck yourself." Thankfully, it ends with a Crowning Moment of Heartwarming.
The way her poor dogs freaked out when she moved, although it's as funny as it is sad.
Her illness in "Texas" and how it was treated. Aside from dragging her off the racetrack when she collapses and having her stay in the hospital overnight, no one seems to pay that much attention to her. She's able to deliriously wander off by herself and end up in a rough neighborhood, and when she returns she wonders if anyone noticed she was gone. This should not happen to anyone, let alone people who are that ill.