If you're building a large JavaScript application, Closure might be your best option given that Closure Compiler (in ADVANCED mode) produces small obfuscated output files that contain only the functions your program uses. ADVANCED mode restricts how you write your JavaScript (but not onerously), but that's where Closure Library comes in: a 1 million LOC "standard library" already annotated for Compiler.

I've found working with Closure Library/Compiler enjoyable, typically more than Python, because the Compiler's type system finds plenty of bugs as I work. It has even caught bugs in my Python code (after I ported it to JavaScript, of course).

There's also good book out there for Closure: http://www.amazon.com/dp/1449381871/