Spoiler Warning/Funny

In their brief Let's Play of Amnesia the Dark Descent, beginning at around 13:00, Josh maneuvres on top of the monster, making it impossible for the monster to hit him. This, together with Josh throwing barrels at the monsters, partly makes for a great Crowning Moment of Funny, and partly removes the feeling of fear from the monsters.
Some of the VATS animations in their New Vegas LP go beyond insane. They're truly a hilarious wonder to behold.
Every person in a room in the White Glove Society's casino is murdered by Reginald, except for one woman that is sitting down at a gambling (blackjack, maybe?) table. Reginald proceeds to casually sit down next to her and attempt to gamble, but the dealer is lying dead a room or two over.
Or this:

"Your cannibal religion-"
"It's not a religion, it's a hobby"

Rutskarn's enraged outburst in the intermission episode where they play Trainz 2010: Engineer's Edition.

Rutskarn: No! No! You are building a game that is literally on rails - literally on rails! It should not be going off the map!
Mumbles: Into the great unknown...
Rutskarn: This isn't even alpha!

- The entire episode could count for one of these, in between the horrible bugs, Microsoft Sam doing narration, the non-stop snark and let's not forget the Hurricane of Puns near the end.
In episode 19 of the New Vegas series after Josh kills ranger Jackson with a sneak attack, he says as he walks out.

Josh: That guy's not a corpse back there, he's lying to you.

New Vegas, Episode 42: Josh is being lectured for causing Shamus' mental breakdown, and in the middle of it he nonchalantly says, "Ooh, there's a frag mine."
- Also, Shamus' Call Back to "I get to decide who has a gun, and it's always ME!"
  - The Great Crash, sent from the cosmic heavens to punish Josh for nearly driving the rest insane during this episode.
  - Once it occurs, the cast make no reference to it or the leadup.
"I would like to assure our viewers at home that no children were harmed in our attempts to murder the children."
Rutskarn avenges Josh screwing with them by doing a dramatic reading of the wikipedia article on the reproductive organs of male reptiles.
Mass Effect 2, Episode 10 comes in with the group realizing that Mordin has apparently grown tired of Josh's struggling through the previous episode and has single-handedly cleared a room normally filled with infinitely respawning enemies.
After one of the many times Josh reloads in Mass Effect 2, Mumbles and Rutskarn imitate giddy schoolgirls obsessing over Garrus.

Josh: I'm not cutting this.

Season 5, Episode 46 was a goddamn goldmine for these.
- Rutskarn: "Would you like for me to predict your behavior minutely down to every tiny and embarrassing detail, or do you want me to have security cameras in your house? Because we can't have both, Mumbles."
  - This is why we can't have nice things.
- Pretty much everything that happens when the Fire Axe is used in VATS, especially the mantis that flew into the air, then fell back only to be decapitated by a second swing.
- "I might have had some bad intel that the final boss was a wicked game of Scrabble..."
- Pick any moment from the Joshua Graham conversation.
In New Vegas, Reginald Cuftbert kicked Waking Cloud into the sun. Don't ask us how, but it was hilarious.
The glorious final three episodes of New Vegas were distilled down to being almost entirely consisting of Crowning Moments.
Episode 7 of Assassin's Creed 2:

Mario: It'sa me, Mario!
Rutskarn: (Angrish)

"I'm so glad you could take time out of your busy schedule to teach a lonely Antlion how to fly."
From the Half-Life 2 playthrough, we get this gem as Josh gets stuck in a staircase battling a headcrab zombie with his gravity gun:

Josh: I need something to throw at this guy... But I don't seem to have...
Shamus: Bullets. You have a machine that can throw bullets at him.

The clips from the failed attempt at playing the first Deus Ex on Shamus' computer during the Human Revolution playthrough.

Rutskarn I KNEW this day would come! I knew the day would come where cyborg satan whispered to me through Shamus' computer and tell me to kill Mumbles and stuff her body in a coffin with Shamus' audio card!

Deus Ex: Human Revolution provided one thanks to the interface, while sneaking.

Josh:Oh Crap.
Grenade: Boom!
He had been trying to holster his weapon.

- The very next episode, while dealing with mines:

Josh: Inventory is full
Mine: BOOM!
Shamus: If only this game had some way to upgrade your...
At this point the stream catches up to Josh
Shamus: ...brain.

- Discussing FEMA's Elaborate Underground Base:

Shamus: Are they launching space shuttles from here? What could possibly need this much infrastructure and support and this many personnel? I understand they had operations in the area, but... What required this level of complexity and involvement?
Chris: ...Have you ever been to Detroit?
Beat
Shamus: Ok, fair enough.

The murder mystery anniversary special is more or less non-stop snarking, with some particular gems sprinkled in.

Shamus: [Steam] Achievement unlocked: You are a pathetic waste of person. Why are you doing this? Go organize the icons on your desktop, you loser.

The original series is full of Hilarious in Hindsight moments. For instance, the swap from Josh to Randy because Josh was insufficently Chaotic Stupid, and the beginning of the fine tradition of Shepard catching rockets with his/her face.
The group imagining how they would behave if they were taken, in episode six of Alan Wake.
- "I maKE pUns to aMUSE my Friends."
During Alan Wake, Chris at one point confuses Stephen King with Stephen Hawking. The rest of the crew start talking about how they could be playing the game as Hawking.