For the setting itself, a test game ended up with Lemurians in a flying giant metal squid attacking a Nazi island by draining a giant emerald shaped like Hitler's head. One cannot help feel a sense of geeky awe.
Again for the setting, the climax of the Invisible Wars, which ended with the Peerage completely obliterating every single clone, brain tape and back-up body that the Nine Unknown Men could retreat to.
On my first run of Genius: The Transgression, the GM planned to have it be a one-shot run and promised to attempt to kill the party. We entered the scene, a dungeon run by near-omnisentient AI from 500 AD based on the four classic elements. These AI believed that all humans were imperfect and must be cleansed. My Genius, a Hoffnung Director, began to out-logic the Conclave of Wind, but was resisted by a lack of perfect logic. Eventually, I pointed out that the Conclave was getting angry and emotion was imperfection, hence it was imperfect. The Conclave then attempted to smite me with a dice pool of 15 aggrivated. Subtracting my defense of 2, the dice were rolled and I hoped for the best. The Conclave got 3 successes, and I had 7 health. Right before it smote, it gave a me a Reason I Suck Speech. I came out of the blast smoking a cigar, wearing a fedora, saying "End ofline, bitch." The Conclave exploded, and the GM ruled that we were now playing a full campaign.
It says really says something about the setting that I can't tell whether or not you're joking about the Nice Hat and the cigar.
We were recently involved in time travel related Hijinx only to find ourselves in the 40s. A bit of poking around revealed the cause: Nazi stowaways who had already left the area. The solution: Send our Mane back in time half an hour to lie in ambush for our own arrival!