Adobe Edge Reflow sounds to be an interesting tool for designers, but the question is, would designers switch to this tool from their Adobe Photoshop or Fireworks? or is that just another mockup tool?

Also, not sure the responsive design cannot be solved with a good set of best-practices for the tools the designers are already using.

The trick is to code it, because, this is where we need to have reusable components (not necessarily at UI-design time).

Anyway, the idea of custom breakpoints is good. I think the 320, 480, 720, 900 are good starting points. Bootstrap does a good job at responsive coding but only for screen size. For application, you need to have a similar concept at the component level for greater reusability.