This necessarily leads to a deep site rather than a broad one, but it works. Don't mix directions. In particular, don't create a design where buttons run top to bottom on the left side of the screen and then continue on the right side of the screen when they run out of room. That's just bad design. Surprises are not welcome on the Web.
Inconsistency leads to confusion.
It may bore you to see all of the pages in a section of your site look the same, but your users will appreciate it. Keep the size, shape, and position of important elements constant throughout a site or section. It prohibits action. Don't use red as a color on a button or link that you want people to click. It will confuse them.