This is a big request: Improve "design in the browser" capabilities. i.e. pushing CSS/HTML and maybe JS changes made in Dev Tools back to the source files without manual shenanigans in the middle. I probably waste more time copying CSS / HTML tweak diffs from the browser back into the related source files than anything else with in browser dev tools. Due to the nature of 'losing changes' if I happen to hit refresh or…
For higher-level languages like Coffeescript or SASS, run a local compiler on the file or function so you can push the compiled code to the browser.
A nice side effect of this approach is that you can use a real code editor instead of the Notepad-style editor embedded in the browser.
In that regard, my #1 feature request for the Firefox devs is to finish and implement the remote debugging protocol [3] and, preferably, work with the WebKit devs towards unifying the two protocols.
[1] https://github.com/swank-js/swank-js