Suppose I have a large but simple object (say, a rectangle) with several small objects scattered randomly on top of it (like a few small circles, ellipses or rectangles).

I want to perform a difference between the large object and the ones on the top, so in the end the large will have cutouts for each of the corresponding individual objects.

I know how to make this one by one, by selecting the base object, the desired form and click on Path > Difference (or Ctrl+-). However, is there a way to do this in a one single pass for all objects ? Selecting all of them does not seem to work, probably Inkscape cannot imagine what my intention could be.

Select everything except on top the one you want to drill the holes in and go Path->Union - then add select the remaining part and go Path->Difference.

Worked, thank you!