I personally recommend looking at OCaml, which has a JavaScript compiler called js_of_ocaml[1]. Using OCaml is a great way to give your projects structure without sacrificing expressiveness--I think it's a much better bet for large projects than something like Dart which reeks too much of Java. The JavaScript compiler is also very good. It compiles down from OCaml bytecode. I've also found the mechanisms for interacting with existing JavaScript libraries relatively easy to use and understand, although admittedly most of what I did with it did not do much DOM manipulation.

[1]: http://ocsigen.org/js_of_ocaml/

There are also some cool frameworks for using OCaml on the server (although I haven't used them myself). So with OCaml you can use the same language for the frontend and the backend, which is always nice.