Nowadays I use tools that do the HTML and CSS for me, such as my WordPress-powered blog, Facebook, Flickr, YouTube, Twitter, etc. But when I hand-code, I first write what I want to say in BBEdit selecting "Use Typographer's Quotes" in the document editing preferences. Then I would uncheck that, select blocks of text, and turn them into headings, paragraphs, block quotes, etc. I would assume I could do the same if I wanted to hand-code (or partially hand-code) a book destined for ePub format, couldn't I? Or I could strip the text out of an ePub book, "educate" the quotes, and then drop it into an ePub generator such as Calibre? I'm just guessing since ePub is very new to me.
P.S. I use the UTF-8 Unicode character set and declare it thus when writing HTML, so the curly quotes and all sorts of other typographical things are not a problem to enter directly using my keyboard rather than escape characters and things like