What is working for me right now is writing first draft all the way through, on my desktop. Then, another two or three rounds of edits to add layers, texture or fix the structural issues. I rest the ms for a week, and then I print it out and go through it on paper. I make the changes on the draft, then read it through on my Kindle, with the old print out and a differently coloured pen to mark any new edits. After that, another rest for a week or so, then a read through and it's off to my Beta Readers. They read it on Track Changes, send it back with comments and I edit--or not--and then have a final read. Then it's off on submissions, else I tweak ad infinitum.
Thing is, no matter how many rounds of self-edits, the ms will have anohter 5 or 6 during the production process, so these days I make sure not to exceed the above--unless I've had a WTF, how on earth did I write THAT in there? moment.