I make all the big changes first. Add stuff in, cut stuff out, rewrite stuff. I have a list of these changes and tick it off as I go (I need my lists!).

Then I run through beginning to end. I line-edit with an eye for things my betas have picked up on (like, in TWW, a tendancy to overuse 'just' that I had NO idea I'd done!). While I do this I smooth over the transitions to and from the new stuff I've added/taken away.

Then rinse and repeat :D