I've got 12 blocks (using a 10" layer cake) made and ironed. I'm putting 3 blocks across and 4 down. I'm going to do the cathedral window around the center block. I think I've figured out how to create another 'center' when I put the rows of blocks together. Got to play with it some more to be sure before I sew. I'm using holiday fabrics and made all my centers white. My first quilt for me.
I saw a block like this tonight that someone had made for a swap and it was a 12 inch block. So, yes, you can make different size blocks.