How many of these things are fundamental limitations of plugins? (Besides the "can start native programs," of course; though I thought one of the Vim-keybinding-plugins had an optional native component that exposed an HTTP interface to allow that.)

I could imagine an extension that's modal and allows its own plugins to be written in JS and then loaded. This doesn't seem at all to be a fundamental limitation, just "Vimium et al aren't designed this way."

Similarly, couldn't an extension use Web Workers to do the intensive processing tasks without blocking rendering, with the only on-main-JS-thread actions being bridging the Web Workers to the DOM?

I guess extensibility is much easier with CLOS methods than with... however people write extensible programs in JavaScript. Prototype hackery? But one could again port CLOS methods to JS as a library, so that's not a fundamental limitation either, IMO. (Maybe the fundamental limitation is the JIT being able to optimize them? I think a normal method cache on the GF might work, though I'm unfamiliar with how JS engines optimize indirect calls in general.)