I found Rebirth significantly easier than the original, mostly because of one factor, Guppy. It's way too easy to get full Guppy if you're careful and maximise your devil room chances. 

Also, somewhat lame but also a real game changer is if you haven't completed any challenges yet, just complete the challenge for Jera (which is fairly easy) it will be the only rune that drops for you ingame, and it's OP as hell, especially if you duplicate the chest chests.