I've recently been working 100% inside of Chrome's devtools using the powerful feature "workspaces". This gives me access to write to any file on the file system. So I've recorded another short screencast (6mins) to show you how to enable it, and quick demo of how I've been using it on my Node projects.
Updated July 21, 2013: I forgot to say in the screencast, you also need to enable Developer Tools Experiments via chrome://flags. Also make sure you check out Paul's comment below with even more useful tips.
There's obviously a lot more to devtools, and I'm running a workshop on debugging in November (or you can book directly). If you'd like to hear about when I'm running it again, pop your name on my newsletter list.
Otherwise, I hope you're able to do a bit less cmd+tab, cmd+r, and a bit more cmd+s :)