I always prefer burning from ISO, it is less stress on the PC, both CPU and hard drives so it is better for slower PCs that might slow down while the burning is taking place and cause the burn-proof to be activated. The one ISO file, even when fragmented a lot, is more "together" than 10-20 different files in a directory so there is good chance you get "hit" in the disk's cache. Also have the advantage of final testing the ISO before the actual burn, why waste even 20 cents media?
Anyway, I do not have utility to check fragmentation of a file, but I have noticed that if you generate ISO with ImgTools Classic, it makes a lot of hard drive grinding and actually takes longer than my prefered way of making ISO: DVD Shrink. The DVD Shrink is 1-2 minutes faster, even with the 1 minute pre-loading in the Open Files mode, and the hard drive is relatively quiet. I do not know if the ISO will be more of less fragmented, you need to check.
To best of my limited knowledge, no ISO making tool will try and pre-allocated the target ISO in one big lump of 4.7GB, hence, there is a need for multiple writes. So, my bet is that ImgTools is writing about 200 times smaller chunks, and DVD Shrink is writing fewer number of bigger chunks.