You can do it, using New Quilt/Custom Set. I think it's a bit cumbersome at first, but once you get the idea it becomes a lot easier. It's best suited to a quilt that doesn't have rows. I've posted one example below (the bottom image).
If you are working in rows but with different size blocks you would be better off adding a border to the smaller blocks when you design them, than using Custom Set. I've included an example of that as well.