Should I just accept it for what it is and not be worried in practice?
My understanding is that "unobtrusive" means a few different things.
One aspect of "unobtrusive" is that websites should maintain core functionality on browsers with limited JavaScript support or none at all. To that end, your concern for this principle should depend on your target audience. I've worked on projects where I knew my target audience well enough that I had the luxury of saying, "if you want to take advantage of this web app, use a modern browser like Chrome, with JavaScript enabled." In this case, feel free to go buck wild with the latest, awesomest front-end frameworks out there.
I've worked on other projects where this was not the case we had to be very careful with our usage of frameworks like Knockout. If you're relying heavily on Knockout to do core functionality in your application, then your application is inherently obtrusive. Whether or not this should bother you depends on your target audience.
Another principle of "unobtrusive JS" is a separation of concerns between JavaScript and HTML. I actually debate how strictly important this principle is. I think a more important principle is a separation of concerns between view model logic and display logic, following the MVVM pattern. Knockout does a fantastic job of encouraging clean separation of view/vm concerns, even if you put a bit of JavaScript logic in your data bindings. As long as it's strictly view logic, I think it actually belongs in the view.