This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Dead Like Me
Seeing how this show deals with death and often its impact on others, the Tear Jerkers are bound to come in heaps at times.
George isn't the nicest person, to put it mildly. She treats everyone with disdain, baits her mother by using the words that she hates, and treats her little sister like Reggie is invisible to her. She only becomes a nicer person after she dies, and realizes how much she has lost.
George had just dropped out of college after a few months because she couldn't handle the constant stress and binge. This means that she'd be lucky to get any job, let alone one at Happy Time. Due to insulting Dolores Herbig, however, she gets the worst job possible.
While at work George actually has a pleasant exchange with a guy after she confesses that a document he needs went down an elevator shaft. He finds it Actually Pretty Funny and asks which shaft it was. Then later, he shows up at her funeral, which leads some to wonder.
George's death. She was just getting lunch, and a guy (actually her reaper) asked her for the time and her name. He then tells her good luck, reaps her, and smiles as the toilet from outer space hits her. She examines her corpse with curiosity and then shock as someone runs through her. We find out later that he's happy because he gets to move on, and George has to take his place.
George's first reap, of a little girl. And if the sequence didn't reduce you to a quivering puddle, the music it was set to pretty much made sure there wasn't a dry eye in the house.
In an early episode where George goes to visit her family and decides to tell her mother who she really is. She plans to tell Joy a story about a moment the two of them shared when George was little, because then she will surely realize that this is her daughter! And everyone will be happy! George walks confident up to the door, but when a mourning, angry Joy opens, she freezes up and the little of her story that she manage to stutter out is barely coherent. Joy ends up screaming at her to get the hell away from here then slams the door in her face. Shocked and saddened by the reality of the situation, finally realizing that she can't ever go back to her family, makes George cry her heart out later on the same day. Rube consoles her despite the fact that she went against his wishes, and the implications, vague as they may be, that Rube had tried the same thing makes it even sadder.
In the season two episode "Always", Rube goes to see his daughter, who is now very old, in a nursing home right before she dies.
In "Reaping Havoc", Betty's ascension into a higher plane of existence. George is very crushed by her leaving, and later, when talking about her alter ego Millie she says she had a sister (meaning Betty) "who was fearless".
George: Why do I keep losing all the things and people that I care about?
Rube: That's what life is, Peanut.
Daisy having to reap a woman killed by the man she was having an affair with.
A man's What the Hell, Hero? speech to Mason for ruining his daughter's birthday party in the season 2 premiere. It was so bad that Mason broke his sobriety.
In the episode "The Bicycle Thief" Mason reaps a gay couple. After the first dies by slipping in the kitchen, he starts begging Mason to make sure his partner doesn't kill himself, all the while Mason knows he has to. Finally the dead man tells Mason that the suit his partner changed into was his favorite and that there were pills in the medicine cabinet that could be used for suicide. Mason, choking up, tells the partner "Slitting your wrist is messy, and that's such a nice suit. Maybe pills?"
Piper Laurie's portrayal of an Alzheimer's patient who didn't realize she was dead in "Forget-Me-Not".
In the episode "Haunted" when George and Mason go to a house on Halloween to reap a soul (who's going to be killed by a serial killer) to find its a little boy who was too sick to go trick-or-treating and that his father was off getting him medicine. Heartbroken, they reap his soul and Mason starts piling his own trick-or-treat candy into the boy's arms.
The scene in the church with Daisy and the transgender woman.
The scene where they revealed Daisy's last thought - "Why did no one ever love me?" It really puts her boasting about all the celebrities she's slept with into a new perspective. Mason's reaction only sealed the deal.
The loss of JD. So soon after losing her sister Reggie loses her best friend.
Reaper Madness, when George's mom gave her those written notes for her teeth instead of cash. Disappointed by the lack of loot, young George tosses the note saying "You are loved" into the trash. Later, her mom finds the crumpled up note. She just falls apart.
In season 2 episode 5, Daisy attends a speed-dating event. Afterward, she finds the quiet man who made the biggest impression on her standing at the edge of a building's roof, despairing that nobody wrote his name down. She talks him down, explaining that she wrote his name down, and offering to go on a date. He accepts, and then looks down over the edge to see people clustering around his body, and he says, "I didn't jump... I slipped."