During Makoto's Help Me!! segment in BlazBlue: Continuum Shift EXTEND, Kokonoe demands that Makoto explain her shelf, to which she responds "You want me to explain furniture?" While this would be a typical response from a ditz and fit this trope under normal circumstances, the look on her face suggested she knew what Kokonoe was talking about, and she missed the point on purpose. Whether this makes it funnier is an exercise for the viewer.
Another one in Valkenhayn's gag reel. Valky describes the legend of the "Sleeping Crimson-Eyed Pigtails" and goes on to mention that even Hakumen pees himself at the mere mention of it. Ragna's response?:
In Duel Savior Destiny when the principal learns that the local nun girl is actually the thief that dresses up like a stripper, her only comment is that her garb violates the school dress code.
In a "Choose your own Nightmare" game called "The Evil Pen Pal", one ending has player character uses his new-found psychic powers to scare and lift said Evil Pen Pal up...and he's sucked into a jet-engine off-screen. The player character calmly says, "Billy flew into the Jet Engine." to his brother when he asks what happened. His brother responds with, "Wow...cool...wanna go home?"
Sissel: So this is an execution, huh? It seems to me there's gotta be a safer way to do it...
Amusingly, he is also completely correct. The man's death happened when dust and faulty wiring on the electric chair caused it to explode, destroying the entire room. It's just that Sissel, having no idea what any of this is, thinks this is the normal way of going about an execution.
In Jolly Rover, James wonders why Melvin is smoking — next to a large barrel of gunpowder:
Melvin: Capt'n Howell hates it too, says smokin's bad to ya health.
One section of the AGD Fan Remake of King's Quest II has Graham attempt to retrieve Neptune's trident from the King of the Sharkees, who's baffled by why he can't use its power. After all, the trident is enchanted in a way so it can only be used by those who possess "good will", and he with his sheer military might and ruthlessness obviously has the greatest will in the kingdom.
Philippine national hero Jose Rizal is an unlockable character in the multiplayer of one of the Medal of Honor games, complete with rocket launcher. The game deliberately misses the point in the name of Rule of Funny since in Real Life Rizal was a pacifist.
In Metal Gear Solid 2: Sons of Liberty This is where the humour in the Otacon save calls during the Tanker chapter comes from. Otacon is trying to emulate Mei-Ling (from the first game) by giving Snake uplifting Chinese proverbs but he doesn't understand their meaning, so in trying to define their meaning he often totally misses the point. It gets to the point where Mei-Ling interrupts Otacon to tell Snake the real meaning of a proverb.
Portal: A running gag with Aperture Science, especially the second game. For instance, as you're about to burn to death, GLaDOS cheerfully reminds you that your gun is designed not to malfunction at high temperatures.
The Investment Opportunity video for the Long Fall Boots reveals that they were invented to prevent the equipment from being damaged. This is demonstrated by showing the little cartoon scientists bearing a broken Portal Gun off on a stretcher while mechanical arms sweep the broken test subject into an incinerator.
Also forms the entire basic premise. Aperture Science invented a working portal device in the 1950s... but never bothered to market it or even announce it to the public, because it was a failure as a shower curtain.
The "comedy" of Mcdougal's racism in Red Dead Redemption is that he tries to sound enlightened about how he discusses Native Americans, while failing to realize just how backwards his views are, to the point where he can't even draw a simple conclusion on why white blood and native blood are the exact same, even after that discovery refuted his own research. At one point, Native teammate Nastas makes a quip about how his people have been suffering ever since white men arrived, which lead to this magical exchange:
Mcdougal: It hasn't been easy for anyone, Nastas. Why, I knew a man in Yale whose father once shot 18 natives in one afternoon out in Wyoming. The man was quite, quite traumatized. He took to lying with choir boys.
Shadow Hearts: Covenant has a hilarious example. Garan attempts to kill the party, however they're a bit more concerned about his appearance, at first. The final time he is encountered outside of a sidequest, he tries to scare the party by telling them that he sent them to hell. However, they all huddle and think that it's the pillow he's floating on. When he asks for their last words, Yuri says, "Yeah - that pillow. Where can I get one?"
In Tales of Destiny 2, Harold, the resident Mad Scientist, asks if she can dissect the most likely to die party member before (what they believe to be) the final confrontation with Elraine. When she's told no one's going to die and thus that's not necessary, she asks whether she can vivisect someone instead.
In Tales of Symphonia, Lloyd is relating stories of extrinsic motivation to Colette and Regal. Despite the fact that Regal CLEARLY tells Colette that Lloyd was referring to the temptation of the food that boosted his memories, Colette seems convinced that it was Dirk's cooking itself, and not the incentive of it, that taught Lloyd how to memorize the Dwarven Vows.
Likewise, in the sequel, Tenebrae complains about the others thinking of him as a stick-in-the-mud. Colette tells Tenebrae that he has no mud on him, and that he shouldn't feel bad. After Emil tells her that, "there was never any real mud to begin with," Colette asks if it was more like a muck or a slime instead.
In another scene from the sequel everyone is guessing what the guardian of the tree looks like. Zelos guesses a hot woman (as is his nature), Presea and Regal hope that it has paw pads, Raine thinks it's a being like a centurion, and Marta just thinks it'll be old. Here's what Colette says:
Colette: So to sum up, the guardian is a wise old lady with a killer body and paw pads.
In Phantasmagoria of Flower View, quite a few characters miss the point of what Sikieiki's trying to tell them, even when Siki's being direct. Even Reimu and Marisa are guilty of this.
In the manga Wild and Horned Hermit, Kasen Ibara puts up a sign saying "Only those who want to die should come here!" in an area filled with poisonous gases and infested with evil spirits. Reimu and Marisa take this literally, reasoning that everyone dies sooner or later, and cheerfully mine the area for gold (which turns out to be made from the evil spirits's greed).
Earlier in the same chapter has Kasen visiting Reimu's shrine, only to find it infested with vengeful spirits and Reimu missing. Then she notices a small gold nugget the spirits were swarming around...and immediately forgets everything about that, instead wondering how Reimu got a hold of it.
In Wario Land: Shake It!, one of the treasures Wario can find is an enormous emerald carved into the size and shape of a melon. His gluttony wins out over his greed, however, as he laments that it is not a real melon.
Don't try to bite it—it'll only lead to heartbreak.
The Thraddash of Star Control have a civilizational cycle of one culture rising up, getting overthrown in a civil war that blasts the Thraddash some 500 years back, a new culture rising up, and so on and so forth (they're up to Culture 18 by now). Culture 14 warned about this 500-year setback, arguing that it really wasn't the best to handle things. The modern Thraddash insists this was proven wrong - the change to Culture 15 only set them back 200 years, maybe 300 tops.