I'm mostly thinking in regards to supporting plugins etc? I'm guessing things can be patched in via the node/jvm bridge that is currently used in the compilation process, but from your Conj talk, it sounds like moving away from the JVM is on the cards (which I'm a huge advocate for with regards to clojurescript).
Does this mean that ideally plugins should be implemented in some v8/nodejs supported language and call remote services to perform a particular operation when requiring JVM/non-nodejs dependent features (As suggested when using the closure compiler in your talk)?