While a website can theoretically look any way you imagine, there are certain traditions that have developed in website design and users have become accustomed to them. Deviating from what a user is familiar with can cause confusion and a reluctance to use the site.
Visitors generally look at the top center of a page first, then look left, then right, then begin to scan the rest of the screen. Important information should be in those areas, that is where users are looking for them. Navigation in particular should be either at the top or along the side of the screen.
Make sure the page has consistent structure which remains the same until the bottom of the page. Visitors use cues such the end of background colour, horizontal lines or suddenly smaller text to tell when a page has finished displaying useful information.
Design the homepage and major category navigation pages to be shorter for easier navigation and scanning, leave the longer pages for articles and content that requires uninterrupted reading. Visitors tend to read content more thoroughly online when the line lengths are shorter, but don't go too far and make thin columns out of the text. About a third of the width of a screen is a reasonable guide depending on the site design.