UX is one of three hundred things programmers have to weigh when making decisions for a business or project.
My claim is that for the user's benefit it may be better to choose a library that sacrifices some benchmark performance metrics like "Time to update the text of every 10th row for 10000 rows with 5 warmup iterations." in favor of startup time and memory. These are the exact same tradeoffs that Seth Thompson mentioned in the video, they can't just be dismissed wholesale.
My question is: how many real apps should make this tradeoff for the smaller library?
I would guess "many more than make it now." Developers are wooed by the columns with a lot of pretty green (myself included) and end up making their app worse because they're optimizing for the wrong thing.
A web site is normally a public-facing collection of HTML and JS where the JS is primarily decorative and the site is primarily page-oriented. Navigation is done via physical pages using the normal browser mechanisms such as links.
A web application is normally a software service that more resembles a desktop application due to its "load once and let the JS take control" architecture. Navigation is normally not done via physical pages, but rather via hash navigation that navigates within areas of the application, as opposed to physical pages. And, you'll see a lot more application-oriented UI techniques like modal dialogs and more elaborate controls (treeviews, listviews, etc).
There are, of course, applications that straddle the line between the two, but it's still helpful to make these distinctions because:
Web sites should optimize for load time first. Otherwise, you're going to have visitors bounce.
Web applications are different, and while they need to keep the load time down, they will most often be already in the browser cache. So, the performance shifts towards focusing more on the actual run-time performance of the application, and that is where issues with raw DOM manipulation may become problematic without something like a virtual DOM or some sort of property caching.