Knockout is awsome. Check it out. You can grasp it over the afternoon and examples of advanced ui-s are interesting and concise.
And then you try to use it for more complicated cases, run into limitations and switch to backbone.
That said, building a maintainable, extensible knockout app is the same as building any other object-oriented system. First, decompose your app into multiple view models (a single view model doesn't have to be bound to the entire page) with clearly defined responsibilities. Combine that with a good Pub/Sub system [1] and you're most of the way there.
That said, it would be nice to see some examples of large-scale knockout apps, as there doesn't seem to be much discussion out in the open in this area. A perfect candidate (in my mind) would be for Steve to release the source code for the knockout tutorial site since that is fairly complex.