Another meta example: This song by The Nobles, "Mandark". It's about how Mandark is Dexter's enemy because he pales in comparison to Dex and just wants to prove that he's also a genius. What's truly sad is that it's prettyaccurate to how Mandark was introduced and characterized (at least earlier on in the show), especially if you've seen "Mandarker" (mentioned below).
The wacky and fun episode of Dexter having to deal with Dee Dee's imaginary friend hanging out with him ends with Dexter wishing away the imaginary friend, and commanding him to never come back again. And he does. Dee Dee runs away sobbing. Then it fades to credits where Koosie just laughs and it suddenly becomes Nightmare Fuel.
Dexter feels so guilty that he finally gives Koosie the hug he's been wanting the whole episode.
'Dee Dee: I feel sorry for you, Dexter. You're like a pickle, sour and all bottled up in your laboratory. Toiling away alone in the dark, searching for answers to questions nobody asked. Locked away from the world, never to experience the true mysteries of life. Well, you can keep your cold, sterile little lab, because for me, the WORLD is my laboratory. Goodbye Dexter, I'll never bother you again. *Dee Dee leaves, leaving Dexter alone in his silent, tomb-like laboratory*
Dad's speech about Pet Heaven in "Filet of Soul".
Mandark's dream at the beginning of "Mandarker".
Dexter's operatic solo at the end of "LABretto".
And before that, Dee Dee wrecking his every invention and driving him to despair, him finding solace in starting his laboratory, and the first time she ever enters his lab...
Its almost worse when you remember that Dee Dee genuinely does not do it out of maliciousness, she's just impulsive and lacks forethought.
The episode "Dee Dee's Tail" is about Dee Dee convincing Dexter to turn her into a horse and, as you can imagine, she is very happy... Until she realizes her brother and her friends just want to use her for rides, not caring if she is tired (even when she is lying down after taking her friends for a ride the whole day, all they do is show her a chariot they want her to pull). Realizing that the people you love just want to use you and don't care for your feelings is really sad.
Dee Dee: This is terrible... First my brother and now my best friends... [crying] I wish someone would help me...
As quoted from Fridge Horror: "When watching Dexter's Laboratory, if you think about it too much, you'll realize what a cruel, destructive scumbag Dee Dee really is. When she's not completely destroying her brother's life's work, she at times openly belittles, insults, humiliates, and abuses him for kicks and giggles." You need only look at such episodes as Road Rash, The Big Cheese, LABretto, Framed, Sister Mom, Dimwit Dexter... you get the picture.
This is doubly worse when you think back to the few times that Dee Dee herself is in trouble. You can tell that despite everything, Dexter has some serious Big Brother Instinct going on, despite being the younger brother who gets put through hell by his sister. That says nothing good about Dee Dee and a lot of good about Dexter.
Dexter's slinking away from his family in Old Man Dexter after being shot down when wanting to spend time with them because he's not old enough is treated to a few oddly long shots without any comic gags in them. Anyone who was the youngest child (or The Unfavorite) in their family can identify with him.
The Gratuitous French episode. He's solved all the world's problems with the term omelette du fromage. One problem— it's not the password of his Laboratory. He panics as the Laboratory erases its memory banks and shuts down.
...if by "shuts down" you mean "blows the fuck up" as Dee Dee taunts him...
Seeing young adult Dexter in 'Ego Trip'. It's really depressing to see Dexter, a boisterous, precocious little boy become neurotic and cowardly. The scene with Mandark whipping him is especially hard to watch.
In his first appearance, Mandark forcing Dexter to shut down his lab—
Computer: Dexter...what are you doing, Dexter?
Dexter: [tearfully] Goodbye, my love.
Computer: Goodby— [is cut off by the sounds of everything shutting down]
—and then after Mandark finds out and laughs cruelly about it, Dexter is shown in bed, crying himself to sleep.
The following morning after that, Dexter tries to say hello to all his favorite teachers. They all respond by coldly shunning him as they go to praise Mandark instead. Dang.
The episode that shows how Mom and Dad met back in the 80s. They participated in a study on OCD and cleaning obsession, with Mom being paired up with Dad who was The Pig Pen at the time. The sad part comes in when you see Mom literally reduced to tears over her inability to get over her phobia, which will ring true for fans who have OCD in real life.