If it were me designing, I would say the comic should be the absolute most important thing on the page, which means it should take up almost all of the viewable area. You don't want a big header especially because you don't want your users to have to scroll down just to get to the content they want; consider a very thin strip along the top with the most essential header elements, and consider using the footer if you want to have some fun with graphical touches, promotional information, etc.
If you're going with a portrait (as opposed to landscape) format for the comic itself you do have to consider whether and how much you want your users to have to scroll. IMHO, since 99% of all people view web pages in a landscape format (crazy TabletPC users like me aside) the optimal way to write the comic is in landscape mode, and in a way that will fit an average 1024x768 screen (minus space for the browser window) without scrolling. If portrait view is going to be your choice though you will have to find a way to strike a balance. I still suggest using as much horizontal space as possible.
Hope that helps