Hello Grant
I just tried it 4 times and it worked every time with R2 (2256)
One was 4048x4048 pixel
It is not very quick, but it seem to work.
What size are you rendering? (how many Pixels)
I don't think you want to go over 4048x4048.
When Piranesi first makes the .Epx file it is large, make sure you have space for it. (my test at 4048 was 140 MB once opened in Piranesi and saved, it went to 26 MB) Also you might try and turning off unseen items or changing your view point to see if it effects it.
If interested, the document I produced for my presentation on Piranesi at ArchiCAD University West can be downloaded here.
http://www.parch.com/temp_piranesi.html
It's a large 9 Mb zipped word document in color.
It doesn't speak to your specific problem, but for those with an interest in Piranesi...
David Pacifico, RA
AC27 iMac i9, 32 gig Ram, 8 gig video Ram