I worked for five years on a proprietary web framework with heavy focus on highly interactive sub-ms precision audio/video and made a good living doing it. A lot of great challenges and I learned a ton about the language through studying the specification, open source libraries, and specifications for various web APIs (websockets, media element, web audio, etc).
However, these types of positions are very rare, you need to be extremely proficient in EcmaScript. There’s a pretty big downside in that if you need to move to a new position, most places generally want you to write “React/Angular/JSBuzzWord” on your resume in the skills section. You’re at a huge disadvantage if you don’t keep current on the flavor of the month.
That being said, if you do land one of these positions you’ll have the opportunity to familiarize yourself with the language on a level that simply isn’t present in the staggering majority of devs.
At my current position I’m more management than dev but we use React/Redux for a lot of projects. However, I personally still write a lot in vanilla especially if we’re doing something unique in node. I wrote a server authoritative game engine recently using horizontally scalable websockets in vanilla (only packages used I believe were uWS and ioredis).