This is something that you might not notice (and it might not even be relevant) if you just need to drizzle a little Knockout throughout your app/site for a little interactivity, but the lack of abstraction really starts to hurt once you go beyond simple interaction.
EDIT: Oh, I should also mention the Virtual DOM, but that's not really that relevant unless you're experiencing performance problems. It might also be very handy for server-side rendering, but I don't have actual experience with that, so YMMV.