Well, any holes that are on the SIDE of the case (regardless how big they are) can't be done directly in the mold, except for if you have half of that cutout in the top and half on the bottom part of the case (which is the case for the USB ports, for example).
Everything else that has plastic surrounded needs to be done with an inlay, and it's never too late to do something like that as that doesn't need a mould change but a new inlay.
Where did you want to have an opening and do you have a heatsink that would perfectly fit in there?