would that make a difference since the files are so large?
Yes, but the more important consideration is how much free space you have. Defragmenting relies on your free space as a "work area" of sorts. In my experience, if you're past 80% capacity on a drive, defragmenting becomes a lot harder. That's not to say that with multiple passes it won't defragment properly, but with such large files, piecing them all together contiguously is going to be difficult without a good chunk of free space to operate with. How full is the drive you're defragging?