Well, I haven't tried enlarging something as large as the Spydie hole, but I have enlarged a thumbstud hole to accomodate a different and quite larger stud on a 440C knife (non Spydie). I used a Dremel grinding bit attached to a drill (didn't have the Dremel tool). It was very slow going for such a small amount of metal. I also broke 2 bits by putting too much pressure.
With the larger Spyderco hole bigger and more robust bits made for drills can be used and you'll probably not break the bit. Go to a hardware store and search for what looks like a cylindrical grinding stone mounted on a metal stem. It also helps if you leave the knife locked open and clamp it still while grinding out the hole.