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This page, as shown in the page image. A resident superhero flips over a room full of bad guys shooting at him. The hero ends up dead, riddled with bullets.
Later on, Dan McNinja has to hunt down the last surviving member of the Belstein family, whose bloodline is the only thing that can defeat a powerful demon. It turns out that the Belsteins had to engage in massive inbreeding to keep the bloodline "pure" so someone could fight the demon... and the last living Belstein is a crippled invalid thanks to that.
A common occurrence on Shortpacked!. Rule of Funny will be enacted, then in the next comic the serious results will hit the characters.
Perhaps the best example of this was when Sydney Yus got herself elected to Congress specifically so she could introduce a bill to shut down the titular store... only to be bluntly informed that she is a federal representative, and that is a state-level matter. "Curses! Trapped in a prison of my own making!"
In Friendly Hostility, Collin gets a part time job as a funny kids show host. When he's publicly outed as being gay, it's shrugged off as a joke at first, until he realizes it will cost him his job. He becomes severely depressed and ends up breaking off his relationship with Fox, and although they try to work it out with a therapist, later canon shows that they never get back together. End of comic.
In Sinfest, there's a Reality Zone. Inside it, characters are drawn with a much more realistic style, and all the normal rules like Rule of Funny or Rule of Cool no longer apply, with characters instead being forced to face reality. The Devil and other supernatural characters all avoid the place like the plague, for example, and Squig (an anthropomorphic pig) turns into an ordinary pig when he enters.
In this strip, a Hydra is attacking by having its heads cut off. This normally wold be an idiotic tactic, as the Hydra grows two heads for every one cut off, but the incessant chopping proves too much for the beast. Why? The Hydra grows so many heads that it can't give enough blood to them all and passes out.
Occurs in The Dreadful, for a given value of "reality". A posse shows up at Kit's hideout. Their arrogant leader threatens and insults Kit while flipping his gun around Revolver Ocelot-style. It looks like an epic gunfight is about to ensue, but Kit simply shoots the hammer of his gun mid-flip, causing it to shoot him in the head.
At the end of one Fruit Incest story arc, Sarah gives everyone a True Meaning of Christmas speech, which later inspires Bernard to leave Simon alone so everyone can enjoy the holidays together. Much later it's revealed that letting a wanted criminal escape doesn't look very good on your resume, Christmastime or not. The Elf Council blames Bernard for all the previous events and unofficially demotes him and his entire group for their negligence.
In Atticus's first Gym Battle in Mokepon, he sends out a Pikachu to fight an Onyx. Sending a cute yellow rat against a fifty-foot rock snake ends about as well as you'd expect. This also plays into the Elemental Rock-Paper-Scissors; Pikachu is an Electric Type with mainly Electric and Normal attacks, while Onix is a Rock and Ground type that resists Normal attacks and is immune to Electric type attacks.
In Drowtales, Shala is subjected to a Slashed Throat, but unlike most examples where this is immediately fatal, because she's a trained healer and knows what to do, she and some helpful nurse-demons manage to stem the immediate blood flow and she's carried to safety by her brother and boyfriend. It looks like she's out of the woods as they make their escape... only for it to be revealed that she actually died from heart failure caused by the blood loss and no one noticed as they were carrying her. Just like in real life, it wasn't the damage to her throat that killed her, it was what the blood loss did to the rest of her critical bodily systems.
Also in chapter 47 the logistics of feeding the massive Sarghress army reach a critical point after their plantations and surface colonies are attacked.