Like Ki, it requires inclusion of a standard library. Unlike Ki, it does not provide alternative data structures in addition to native JS values; it only uses native JS values. LispyScript also does not support embedded JavaScript or being embedded within JavaScript. But LispyScript currently has better docs, including a page to try it in the browser (http://lispyscript.com/tryit/).
I mean, there is a whole long list of benefits of functional programming, immutable/persistent data structures, macros and so on. But Lisps and functional oriented languages (like Roy, LiveScript) are also unfamiliar, not supported in your favourite IDE, make you think in a way you're not accustomed to and eat your kittens for lunch.
You have a chance with ClojureScript if the backend is in Clojure - other than this there is just no way to introduce something like this.
As for usability, ClojureScript works very, very well. Async is well implemented (if you like CPS model), JS scoping is fixed and so on. LiveScript is also quite usable, although it lacks source map implementation for now. Backcalls make async nice but stay close to JS, currying and partials are nice, easy object cloning makes up for inherent mutability. For my personal projects I use LS instead of JS or Coffee exclusively now.
But they are completely unusable in enterprise environment. And probably won't ever be. It would also be very hard to find a team which would like to adopt them without knowing them beforehand (rightly so, IMHO, because transitioning to another paradigm - and benefiting from it - is not a trivial matter) and about as hard (or harder) to find a team where they are known already.
Your best bet is probably to contribute to LightTable a lot and seek a job in Clojure oriented start-up if you want to use ClojureScript at work.
