Melodyne is best used in small regions, although I have blatantly abused this at times just to stress-test the software, so it will do as much as your computer can handle. Something important to bear in mind is that SONAR does not delete audio on you... when you bounce a clip, SONAR renders it and creates a new file. The original is always there for you. I too have noticed that Melodyne seems happiest when you create small regions and bounce them. When finished, bouncing the final entire track to make a new clip is also common.
FWIW, (manually) saving a project seems to also make editing run more smoothly. Melodyne edits are actually saved within a cwp file, so saving prior to and after bouncing edits seems to make SONAR happiest (the cwp actually expands and contracts in size storing/releasing Melodyne edit info).