"It depends" - the only viable answer :D But seriously, it largely does depend on the behavior of your application.

If you're going to use Knockout to provide wiz-bang editing and binding on single page (as opposed to a slew of jQuery code everywhere), then you might not need much more than Knockout.

If you're going to be creating multi-page JavaScript applications within a single page of your site, you should look at combining something like Backbone.js with Knockout, using the Knockback library I linked to in that article.

Alternatively, if your looking for good structure for JavaScript applications in general, I have another post that introduces a few of the concepts and links to some great resources, here: http://derickbailey.lostechies.com (unfortunately, I can't get the exact URL at the moment... site seems to be slow / not responding. just look for the "Intro to composite JavaScript apps" post)