So, it seems that you want to do 2up printing...
but you don't just want the whole page scaled down (whitespace and all)
...but just the relevant text region and maybe some whitespace.
I just tried the following with a PDF printer like PDFCreator.
Suppose I have a PDF file with large whitespace borders...
Using Acrobat reader, print to another PDF (without scaling) to pages whose size is smaller than letter size. (In Windows, choose Print... then Properties (for the selected printer)... then Advanced... then choose a smaller paper size. (You should be able to get a thumbnailed preview of the croppped pages in Reader's print dialog.)) This new PDF will have smaller page sizes with the same size text with lots of whitespace removed.
Now open this new PDF in Acrobat Reader... print 2up (which will be scaled down) on letter paper. Not quite automatic... but it seems to work.
Alternatively... here are some other ideas...
If you can generate the individual pages as images,
you could write a script (in perl or python or bash) to use imagemagick
to make images of the desired pages... then print those. (Imagemagick has operations to crop out regions or "trim [boundary colors]".)
If you can generate postscript, you could try to print to postscript
(create a printer with a postscript driver [even if you don't have the printer]
and tell it to print to a file). Then do a crop (e.g.
http://www.perlmonks.org/?node_id=10635 ) on the resulting file.
Then print 2up (e.g.
http://www.tailrecursive.org/postscript/nup.html ).
This could be automated using
http://pages.cs.wisc.edu/~ghost/redmon/index.htm
There's probably a ghostscript solution:
http://pages.cs.wisc.edu/~ghost/doc/other.htm
Hmmm... .. check out
http://www.mscs.dal.ca/~selinger/upprint/ (probably some work needed to use this in Windows).