I want to move a large premiere project I've been working on from my C to an external hard-drive.
Will the change in letter name (C:\ to E:\) mess up my project? Will I have to re-import, etc?

Check out this thread, especially Harm Milaard comments:

http://www.dvinfo.net/forum/adobe-creative-suite/482716-moving-complete-project-external-hd.html