No it is not a problem. If you defrag with the microphone plugged in all that will happen (on XP anyway) is that sound-related files, e.g. .wmv, will be cached then moved to the outermost sectors of the disk during the defrag.
Yes I guess, rather than fly into a panic and think that you have lost all your stuff on your computer and spend hours deleting temporary files and cookies etc, that would just be a complete waste of time