A Simpson causing the death of a Flanders family member stops being funny after the episode "Alone Again, Natura-Diddly (only replace "Marge" and "Ned" with "Homer" and "Maude"). Furthermore, at one point in the THOH segment, Moe calls up the (recently widowed) Maude in an attempt to stalk/date her. In the latter episode, after the funeral, Moe then begins to "console" Ned by telling him how hot she was and that if he had died instead, he would be all over her. This angers Ned so much, he starts punching Moe in the face repeatedly as the bartender reacts gleefully, saying for him to "send me to Maude".
Even worse is when the Y2K bug takes over, Dick Clark says "Oh, no, it's happening" and melts to reveal a robotic skeleton (a la the T1000 in Terminator 2: Judgment Day). Back then, it was just a joke about Dick Clark's seemingly perpetual youth. Now, it's not so funny thanks to the stroke he had in 2004 and his death in 2012.
Nightmare Fuel: Few things are as disturbing in The Simpsons as Homer and Bart exploding in deep space, even if it happens off-camera.
The "Life's a Glitch, Then You Die" short in general, since it takes a very real concept (computer glitches) to an extreme (the breakdown of society).
Values Dissonance: The final few minutes of "Life's a Glitch, and Then You Die", where Mel Gibson and Ron Howard are among the A-listers on the Mars rocket, while Spike Lee is on the rocket to the sun. The former can be excused at the time on account of having been a recent guest, and still being a few years away from his public fallout. Ron Howard is a little more spotty though; while he has had a reputation as being a perfect gentleman, even then he was hit or miss at the box office, and his better films still being a couple years off. The worst that can be said about Spike Lee, by contrast, is his oft-polarizing nature, but few can deny his level of artistic integrity, or his level of accomplishment. The writers at least have regretted putting him on the latter rocket in retrospect.