ES6 stuff with Babel, Webpack, plus maybe gulp is all digestible, if you are otherwise rolling your own site-specific frameworks. If all you have to deal with is tooling, and you get decent modules/imports from Babel, then the learning curve is worth the cost (because benefits are good). I'm doing this with a D3-based project and I'm happy with what I can do, but the project scaffolding is still a bit much.
Beyond that, about all I want to have patience for is (a) test running tools, (b) mockup/patternslib (because I work in Plone all the time), (c) (maybe) web components (because they might be standardized someday).
Adding react/angular/whatever to the mix makes my head hurt, and IMHO I'm a pretty darn good JS developer (as far as core/new language features and idioms are concerned).