Oh, my goodness, your brain is stuck on thinking of 4-squares sewed together as being a block (which it is), but your brain is not recognizing that ultimately what you have is a bunch of squares sewed together. Sew pairs of squares together and sew them into the gaps. When I refer to a "pair of squares", I mean one square against the quilt and the other go the outside. If you find your gap measurement is something slightly different than the measurement of 2, 3, or 4 pairs of squares, then it's math time. You can make one or two pairs of squares slightly larger or slightly smaller than the others and the eye won't notice. For example, if you are using 2" finished squares (2.5" cut) and you need to fill in 6" of space - well, that's three pairs of squares. But, if your gap size is 5", then you will need to trim the pair of squares width. You will need 1" less, which could be 1/2" from two pairs or 1/4" from four pairs. I'd be tempted to do the 1/4" trim and spread it out, taking 1/4" from pairs separated by a couple of full-sized pairs. Be scant when trimming because you don't want to take off too much and in the end you can always sew a deeper seam to make things fit. I might even be tempted to trim with width of more than four, just a tiny bit like 1/8". It would be negligible.