Well the issue at hand hasn't been given some absolute clarity, you simply said that it won't seem to launch from USB and that large ISO's are split
and I play plenty of split ISO's which makes sense if your USB is formatted to FAT32 leading to 4GB splits being necessary
Are you mounting from webMAN or Managunz? I am not most familiar with the 2 but someone else may be... Also have you tried mounting from Multiman to see if it even allows the game to mount or perhaps throws you an error instead?
Could he possibly use NTFS drive instead?
Also upon searching Google for errors that are related to the PS3 version of Vanquish users report that they have a lot of issues with game freezes