I used to hear that it was a good idea to defragment your hard drive in safe mode as it would be able to defragment more of the drive. I just did a defrag and decided to check on this and there is not much that is not defragged so I would not worry about it. Here is what Microsoft has to say about defragging as well as info on the Master File Table :
The following files are permanently excluded from being defragmented. These files may be displayed in the analysis report as still being fragmented no matter how many times you defragment the drive.
Moving the following file can cause desktop problems, if the Recycle Bin or the Recycler folders are removed:
Moving the following files (if present) can cause desktop problems:
The following files are unmoveable system files. They are always displayed in green in the defragment analysis display:
NTFS Master File Table (MFT) and Reserved MFT Zone: Usually contiguous at the very beginning of a NTFS volume but can become fragmented if many files and folders are added to a volume.
NTFS Master File table Mirror (MFTMirr): Usually located in the middle of a volume and is already contiguous.
Virtual Memory Paging file: Used for temporarily swapping pages of memory to disk.
Adjusting the MFT
Although you cannot defragment the MFT once it becomes fragmented using the Disk Defragmenter, there is a way of preventing MFT fragmentation, or at least reducing the possibility of it becoming fragmented by reserving space for it ahead of time.
To determine how large the MFT is, how many fragments there are, and what percentage of the MFT is in use on an NTFS volume, perform a Disk Defragmenter analyze operation to generate a report. View the report and look for the following section under Volume Information:
Master File Table (MFT) fragmentation.
Use this information along with the following article in the Microsoft Knowledge Base to adjust the NtfsMftZoneReservation value, back up and reformat the volume to create a contiguous MFT using the higher zone reservation space, and then perform a full volume restore: