This one stuck with me, as it both surprised me and made me appreciate the Fallout series.
I'm heading south, at night, towards the direction of the Dunwich building. I'm traveling through a rocky passage when a hostile comes on my scanner. At first I figured it couldn't too big of a deal since I was level 8-10 (I forget), to my dismay, when I turned the corner, it's Deathclaw and I have nothing more than light weapons. Seeing no way to harm it, after using all my ap in vats, I run towards probably the worst possible safe haven, the Dunwich building. The Deathclaw trailing behind drains my stimpaks to zero, but fortunately I get into the building without it entering as well.
At this point I had a choice, either risk going back out, or continue through the Dunwich building; hoping to find some stimpaks for my injured self. I chose the latter knowing full well I had nothing in my inventory.
In the end I fought through the Ghouls with what little amo and supplies I had; using whatever supply I came across to the best possible use. This was probably the only time in Fallout that I truly felt it was a survival game without any mods. Stuck between a deathclaw and an army of ghouls you had to weigh your options without the game giving you a note or quest to hint you.
“We can only see a short distance ahead, but we can see plenty there that needs to be done.” - Alan Turning