This'll be something of a first, as I've used the open-source desktop publishing app Scribus to assemble the cover art (although not the interior; I'm still using Word for that). My previous efforts were all Photoshop, but this time I did the graphics alone in Photoshop and added text and layout through Scribus. The end result I exported directly to .PDF and uploaded to Lulu.com.
It astonishes me how easy it is to do so much of this stuff now. It's desktop publishing in the most complete sense of the term. — not just the design, but every single stage of the publication down to the fulfillment. I'm still working on the promotion end of things, but I figured that part would always lag a bit.