Any longtime fan of Bethesda sandbox games knows this, but if you're a noob it bears repeating.
SAVE YOUR GAME RELIGIOUSLY.
And don't just rely on the quicksave or autosaves either. By all means, use them, but make REGULAR hard saves as well.
Booted up my game tonight after work to find my quicksave had become corrupted somehow. Fortunately, I had a hard save from just 5 minutes earlier, meaning I did NOT have to re-wire the entire Starlight Drive-In control room for a 2nd time, nor did I lose my 150+ hours of gameplay.
You've been warned, SAVE YO GAME LOTS!!