Number of files on the drive shouldn't matter that much, actually. In a single folder is a different matter, of course (for that you definitely want to disable

Number of files on the drive shouldn't matter that much, actually. In a single folder is a different matter, of course (for that you definitely want to disable 8.3 compatibility). But the only way I can imagine right now where the number of files on the drive makes a difference would be where you crammed the drive almost full, resulting in a very fragmented MFT (normally the file system tries to keep space for growing the MFT, but not if you try to fill that space with data, too).