If it's been a long time, you should definitely take a look again at components, which really feel like the thing knockout has always been missing.

All bindings are still fired upon applyBindings, but I haven't encountered issues here - it's still once on page load, and I can't imagine that it's much different than building the DOM initially using handlebars or react.

I would surely make time for KnockoutJS. But currently I have been following flux which is quite easy to implement althgh I am still not sure how it works with routing, 3rd party libs like some charts etc.