I have to say I just cannot get used to using the Reader in landscape mode, not even for PDF's. Not sure why this is the case, but I guess I feel I should be able to see the whole page at once. Now if only the device was able to scroll a document's page like on a PC, then I could use landscape mode without any objections.
Since I'm still young (fairly so) and a little near-sighted, I stick with portrait mode and small fonts, though my wife tends to prefer portrait with medium fonts (no idea why, but she's happy so I don't push my my tendancies off onto her).