Buying Fallout 3 GOTY.
On my first New Vegas playthrough, I went down to the East of the Cemetary at Lvl 1, having ignored all the quests. There was a Giant Radscorpion glitched into the mountainside, so I shot at it. Eventually, I crippled it's Right Claw, which caused it to glitch OUT of the mountainside and murder me in two blows. Results: I now doggedly stick to the quests until Lvl ten, and fear Radscorps more than DCs.
Any Frag Mine hidden under an orange cone. I never quite get those things.
In Fallout, I was smart and mined the Radscorpion Cave entrance so I wouldn't have to fight them all...but I was inside the cave when the bomb went off.
I attempted to engage The Master while wearing Tesla Armor & armed with Spiked Knuckles.
Every time I have to fly into a [censored] tunnel in one of the Ace Combat games.
In ACZ, I once engaged the final boss in an F-16XL.
There was also this one time I built a 1200T mini-destroyer armed with missiles, guided torpedoes(both antiship and antisub), and AA guns in Naval Ops: Warship Gunner 2. It was a surprisingly solid little ship for so late in the game....then I ran across a flotilla of (fairly common by now) battleships you can't lock guided weapons onto.

-Nukeknockout