For me, it was when I was playing TF2. Everyone was playing normally, but then someone came on with the ability to play music through his microphone. We were enjoying it, or ignoring it, but then we heard the beginning dialogue of a rather infamous song, Baby Got Back. I never imagined it possible for so many people to spam the "Yes" button when "Mute and Gag" vote came up.
Portal and Portal 2 are the funniest games ever. The Joker dialogue in Batman: Arkham Asylum and Batman: Arkham City is really funny too.
Battlefield 3 I once had an infinite ammo. I could shoot how much I wanted but the "Bullet count" did never go down so I never had to reload. And yes I could kill enemies with the bullets. Sadly enough was that the one and only time that it happened But I love BF3 otherwise
Orbiter (an obscure spaceflight sim)... I was flying a Delta Glider IV spaceplane with 5 people inside. I was playing around with the buttons in the cockpit, and found one that said UNLOCK CABIN. I pressed it, and the whole windshield blew off! Needless to say, all 5 were dead within seconds, as I was in space. I feel nauseous when I think of TF2...
Halo 3. (Back in its prime, 2008 days) After a host migration I was in a ghost and it spawned me outside but I could still drive it so bascially I shot Ghost "bullets" with my gun and when I ran it made the Ghost vehicle 'moving' sound. Hopefully this makes sense. Also The Amazing Spiderman Videogame is actually quite enjoyable and funny. I recommend it
