What version of Windows are you running?
Have you tried to run Diskeeper in Safe Mode Windows?
Have you tried to run the Windows Defragmenter?
Do you have an NTFS file system configured?
When you run a defragmentation of any kind, you will want to stop as many programs as possible from running and altering the file configuration that you are attempting to defragment. I recommend trying to run the software within Safe Mode Windows.
http://windows.microsoft.com/en-US/windows-vista/Start-your-computer-in-safe-mode
This will allow you to eliminate many programs that would prevent these actions from occurring properly. Things like power managment and screen savers will present an issue as well. If the machine is set to go to sleep, defrag will not run. Consequently, if there is a screen saver set, the machine will never finish the defrag, usually, because of processor time that is being used by attempting to run both cpu intensive programs.
The NTFS file system technically does not require defragmentation. The way the file system is configured fragmentation should not occur. However, this is in a perfect world with always perfect conditions. The longer you allow your system to go without reformat or "cleanup," the slower the system will respond when dealing with the file system. I'm not talking 6 months time, I am talking years. There are people that have owned their computers for 10 years and wonder why it performs slowly. You have to reformat from time to time. Fragmentation also depends on the level at which you install and remove software and files. Download operations, such as music or movie, can cause fragmentation if performed at a high level.