The idea behind using a 2nd drive would be to eliminate the possibility of hard drive failure. The ISO is stored on your hard drive, and perhaps their is an issue reading a file that big from the hard drive. Perhaps the data is scattered out all across the drive, and so you HDD needle is wandering all over the place trying to keep the video playing, but it gets over-burdened.
As for the video card idea, that's no good. If it was the video card, you'd have the same problem when playing from an actual blu-ray disk. It wouldn't be limited to just ISO files.
"In practical life, the wisest and soundest people avoid speculation" -George Earle Buckle