Since installing OSX Lion I've found that OmniGraffle has been, well, pausing from time to time. Which is odd, since it always used to run quite quickly. After some fiddling around and then an email to the Omni Group support, they pointed this out:
Apparently the QuickLook Preview is generated every time that file is saved. Lion constantly saves the file as part of its automatic save function (you don't need to save files that are correctly using Apple APIs for document save, it saves automatically) and this means that OmniGraffle is constantly updating it's QuickLook image. For large files, this takes a fair amount of time.
Which correlates with my experience, small files didn't have a problem but bigger files did.