I square up the final quilt before binding. I use a reference on the body of the quilt to keep things consistent. for example, instead of assuming my border is straight and just trimming it along the edge of that, I will put my ruler on an inside square and trim to 6" (or whatever) outside of that inside seam. For this reason, if I want a 6" plain border, I often will make it a bit wider so I have plenty of room to trim up to the desired size in the end. My piecing is generally more true to square than the borders.
But, if I had a whole cloth kind of quilt with no standard reference line to square to, I would have an anxiety attack and just use the "hope and pray" method of cutting!