A big design mistake was the global cascading/inheritance system. It's a huge pain to write CSS that doesn't leak into nooks and crannies where it shouldn't. CSS is supposed to be modular, but you can't just import someone's stylesheet (e.g. for embedding something in your page, like a video player) and trust that it won't override everything around you, intentionally or accidentally.

More than that, CSS was designed for "styling documents" — the idea being that you could display the same document with different stylesheets, sort of like themes, and so the stylesheet obviously had to be separate from the document. But almost nobody who uses CSS these days do it to "style" anything, let alone "documents". One particularly egregious issue coming from this design is the attempt to separate layout from content, when in truth layout is content, and for pretty much any application today, the style is also content. We're well beyond the point where an HTML document can be "semantic".

Shadow DOM may be the way forward in the future, but CSS Modules is a nice stopgap solution, at least, and you can use them with React + PostCSS (+ SASS) + Webpack in a nicely seamless way, without requiring any browser support.