Via his blog, Bryann Lee O’Malley shades the wisdom of cartooning and good balloon flow:
Try to avoid layouts that make as little sense as this one. Also try to avoid hiding your weak layouts with trickery, such as arbitrarily wider gutters (top right) or dropping panel borders to create the illusion of clarity (bottom middle).
A key lesson is: try to attach your balloons to the tops of the panels, especially the corners, because that makes everything a hell of a lot easier both for you and the reader.
BTW, some might argue that the rule breaking first example (from Scott Pilgrim #3) still has a lot of energy and charm in its very awkwardness.