Usually, a designer strives to think outside of the box. While this is what we (should) do best, when it comes to the web, sticking to standards will make it easier on the user. Magazines have a table of contents near the front, and page numbers in the corners. Newspapers are divided into sections, headlines span across entire articles, and the largest headline is the most important.
Similarly, web sites have certain elements people look for, and designers can use this fact to their advantage. When a user navigates to a site for the first time, they expect certain standards. They expect the navigation to be confined to a section of the page, some sort of header on the top, and a logo or company name on the top right. When a site meets these expectations, the user can easily navigate, and know where they are at any given moment, without having to search around for the button that will take them to the contact page. Ebay is an example of following this set of standards.
Designers can find this standardization limiting on their part, but they still can create unique and beautiful sites within these guidelines (thinking outside the box?). These standards are not rules set in stone, they will change through time, but for now, if you want maximum usability on your site, you should consider following these guidelines.
Finally, thinking outside of the box is never a bad thing, as long as your ideas work. More specifically, depending on the purpose of the site and target audience, you may want to try something new. So long as the learning curve for the user is worth the visual interest or purpose of the site then go for it. Ideally, your design will require no learning curve at all. A site I came across recently, JLern Design, is an excellent example of a new form of navigation that is not difficult to grasp (although its downfall is slow loading time, which is another issue).