Snoopy, Come Home - especially the farewell party, at which Charlie Brown is supposed to give a speech but is too emotional to say a single word and just stands there with tears running down his face.
Charlie Brown's failures at something become expected after a while, but when you keep seeing it for decades, and even up to the strip's end, you tend to really feel disappointed.
One of the most heartrending examples is one of the simplest when Charlie Brown is at a bench at lunch all alone and sees the Little Red-Haired Girl and he can't get the nerve to approach her:
Charlie Brown: It's stupid to just sit here and admire that little red haired girl from a distance. It's stupid not to get up and go over and talk to her. [stands up] Charlie Brown: It's really stupid! It's just plain stupid; so why I don't I go over and talk to her? [sits down in utter personal defeat to the point of tears] Charlie Brown: Because I'm stupid.
Notable in this category is the 1969 storyline in which the Little Red-Haired Girl moved away, and Charlie Brown was depressed not only because she was gone, but because he was never able to work up the courage to even tell her goodbye. Even a ski vacation he took with Linus and Snoopy not long afterward provided any respite from his heartache... because guess whom he saw at the ski resort?
She apparently did move back at some point, though it was never explicitly mentioned when or why.
The strip where Peppermint Patty tells Linus how she broke down crying when seeing the Little Red-Haired girl is devastating, especially since that's all that happens in that particular strip; there's no punchline or "smiles-through-the-melancholy" comfort to ease how unhappy she is:
"I stood in front of that little red-haired girl and I saw how pretty she was... Suddenly I realized why Chuck has always loved her, and I realized that no one would ever love me that way... I started to cry, and I couldn't stop. I made a fool out of myself, but I didn't care! I just looked at her and I cried and cried and cried... I have a big nose and my split-ends have split-ends, and I'll always be funny-looking and I think Im going to cry again..."
Lucy has often made no secret of the fact that she wished she were an only child or at least had a sister. In a 1959 story arc published shortly after Sally's birth, this hurt Linus so deeply that he decided to run away from home (though he didn't get far because he wasn't allowed to cross the street alone). While Linus often has his own clever way of dealing with his sister, seeing how badly Lucy hurt his feelings this time is tough. In the final strip of the arc, Lucy, seeing Linus in tears, apparently realizes she went too far, and actually apologizes to and comforts him, saying, "We're part of the same family... brother and sister... blood relatives." The heartwarming moment doesn't last, because her next words are: "No matter how you look at it, I'm stuck with you!"
The 1966 storyline in which Lucy and Linus' father got a new job and the family had to move away - especially when Linus gives Charlie Brown his blanket to remember him by. Even Schroeder seemed to miss Lucy. As it turned out, though, Mr. Van Pelt changed his mind about the job and the family moved back just a few days later.
Marcie: Everyone's gone home, sir. You should go home too, it's getting dark. Peppermint Patty: We had fun, didn't we, Marcie? Marcie: Yes sir, we had fun. Peppermint Patty: Nobody shook hands and said "Good game".
The last new Sunday strip, which is also Sally's final appearance, has a similar wistfulness. Charlie Brown is cleaning their mailbox for a love letter he knows will never come, when the rain returns
Sally: Aren't you going out to get the mail? Charlie Brown: Not while it's raining. When it's raining, the only letters you get are the ones that say, "I never want to see you again!" Sally: You seem to know a lot about love letters. Charlie Brown: If I ever got one, I don't know what I'd do
The ending of the "Baseball Game" sequence in You're a Good Man, Charlie Brown, where Charlie Brown writes to his pen pal about the baseball game he lost, only to mournfully write a new letter with a completely different subject while he fights back the tears.
Any time Charlie Brown is the victim of bad luck. For example, Charlie Brown not getting any valentines, not getting an egg from the "Easter Beagle", being unfairly blamed for losing the homecoming game, and having his dream girl stolen from him twice (the first time by Linus, the second by Snoopy). It becomes bittersweet when he actually DOES win a motocross race.
The occasional references to Peppermint Patty's Missing Mom. A self-described "latchkey kid," she frequently loses sleep waiting for her dad to come home, causing her to zonk out in class, according to Jean Schultz. Charles Schultz never specified whether her mother was dead or simply missing from her daughter's life; to a query on why she can't stay with her mother while her father is out of town, she replies with a simple, "I don't have a mother, Marcie!"
Marcie: I think I'll go home and paint my tongue black.
Most of the strip's storylines put Charlie Brown through the wringer, but a few stand out as exceptionally cruel. One of these is the two-week arc in which the gang, egged on by Linus, decide to throw him a testimonial dinner to show their appreciation for all he does as the manager of their baseball team. When Charlie Brown gets the news (via a phone call from Peppermint Patty), he's so surprised and delighted ("I'm smiling!!!") that he looks, in Sally's words, "like [he] just swallowed a chocolate cake." At the eleventh hour, however, the kids realize they're being hypocritical—they all think he's a terrible manager and player and they can't say otherwise and maintain their integrity. They proceed to call off the dinner moments before it begins, leaving Charlie Brown (in the last panel) besuited and alone at a table, surrounded by balloons and streamers.
Charlie Brown: I would have enjoyed even a hypocritical dinner.
The 1990 TV special Why, Charlie Brown, Why?, which tells the story of a pretty little girl named Janice, who not long after becoming friends with Linus, is diagnosed with leukemia. Linus is especially hit hard as he has gained feelings for Janice, and is scared over whether she will survive her illness. Throughout the show, Janice suffers a number of health setbacks, endures bullying from a classmate (who until he is told to walk a mile in her shoes refuses to understand her illness) and a lack of empathy from Lucy (she "fears" that Janice's illness will spread similar to how the common cold does) and jealousy from her two older sisters, who are healthy and feel ignored. Eventually, there are tears of joy as Janice returns to school with a full head of long, blonde hair — she had lost her hair earlier due to chemotherapy — and seemingly in full health again. The special ends there, but it leaves her future to the imagination of the viewer. Either Janice will remain healthy, or her cancer will eventually come back, or most tearjerking of all, it may be that she isn't cancer-free, but that her illness is terminal and that she and her parents have decided to stop treatment, knowing that death is imminent. Indeed, Janice is a one-time character who is neither seen again nor referred to in future specials.
In one series of strips, Peppermint Patty and Marcie invite Charlie Brown and Snoopy to play a type of hide-and-seek called "Ha Ha Herman." As Patty and Marcie search for the hiding Charlie Brown, Marcie asks Patty if she likes him; Patty denies it, asking how anyone could be in love with "boring, dull, wishy-washy Chuck"...right next to the bush Charlie Brown is hiding in. Cue a heartbroken Charlie Brown emerging from the bush and leaving with Snoopy, as a horrified Patty desperately tries to explain herself. The next few strips reveal that both a depressed Charlie Brown and a guilt-ridden Peppermint Patty have taken to their beds because of what happened.
Charlie Brown: Ha ha Herman...*sigh*.
Life Is a Circus, Charlie Brown: Charlie realizes that Snoopy hasn't come home and later watches him board a cart as the circus prepares to leave town. Made even worse when he calls out to Snoopy but the gate slams shut before he can escape. Snoopy's reaction sells it, as does Charlie saying "Dognapped!"
Later on, Snoopy and Fifi run away from Polly. Fifi decides to stay with the circus because it's her life, leaving Snoopy to board the bus alone and heartbroken.
The 1990 October arc involving Marcie's forceful parents.
One strip in 1966 shows Charlie Brown waking up to smell smoke in the air, right as Snoopy starts banging on his door. He rushes out to find... Snoopy's doghouse up in flames. All he can do is hold a deeply upset Snoopy.
Snoopy: My books! My records! My pool table! My Van Gogh! Charlie Brown: Good grief!
The very next strip is even worse; the first three panels are of Snoopy inspecting the burnt-out shell of his former home, while the last one is of him crying.