I'm sure someone's done this before but here's a neat worldbuilding idea:

Humanity finally expands into the stars, only to find abandoned cities from a hundreds of thousands of species on all the worlds we visit. Some systems have half finished mega-structures, some have have barely entered the industrial revolution.

The only common factor is that all signs of habitation seem to have ended at the same time, adjusted for light delay.

Humanity is alone in the universe, and something happened to make it that way.