What can I do about a Rough opening that is REALLY out of square?
You can order custom size window at homedepot , low's or Pella etc, which is more expensive than standard size. If feasible and depend on the interior and exterior of your building and compatibility with other window sizes, I suggest you make a rough-in for 5'0x3'0 window, that is standard size window, and after the installing the window you can correct the imperfection by triming the window. Ofcourse the answer could be easier if you post the picture of your building and the area that you have problem with.