As important as the main navigation is for a website, I've be taking the approach recently of intentionally leaving it out of designs until very late in the build.
This seems to help everyone involved in the project really focus on the user's journey through the site. Not just ensuring a user can find the information they want, but find it in an intuitive and natural way.
I'm currently working on a redesign of a charity website, where a key objective of the new design is to increase the number of donations from supporters.
So, we haven't looked at the main navigation yet - and I would be surprised if it didn't end up with a prominent Donate button in there. But in real-world use, a typical supporter might well not be coming to the site with the express intention of making a donation. Their journey is more likely to be to first find out more about the charity, the issues they are trying to address and the successes they've had so far.
The user journey we've been developing has focused on a person coming to the site, being shown a summary of the history of the charity, their current campaigns and some issues that might directly affect that person. The expectation is that most people will be interested in one or other of these sections and would want to read more about this before considering making a donation.
Once into the section of their choice - the supporter is given the information they'd expect to find about the charity or their campaigns, and then given clear options after reading the content about where they might like to go next. This might be another information page about the charity's activities or to now make a donation.
It makes the decision making process much easier for supporters. They make an initial selection as to the type of information they are most interested in, and then guided through as much additional supporting information as they want - before they feel comfortable about making a donation.
Visitors are never expected to return to the main navigation and make another decision about where to go next because they've reached a dead-end on their current content trail. Even the donation forms are embedded on the page, so there's no wait for a page to reload, no change in context and the whole process of research leading into the making of a donation feels very natural.
This isn't to suggest the main navigation isn't important. There's all sorts of reasons why it will still be used - but in the design process it's too easy for those very familiar with the site to go from section to section of the site via the main navigation, and not put themselves in the shoes of our users with regard to how content might actually be used and interacted with.