In Diskeeper, go to Change Your Settings:
Set defrag Priority: Manual to Highest
Set defrag Method: Manual to Quick Defrag (afterwards to Max Disk Perf)
Set Performance data options: do NOT Allow (for first, quick defrag), afterwards, click it.
Switch off your AntiVirus software, isolate that Disk (or the whole PC) from network-access.
If you can, temporarily export some data to another disk to free up space.
Diskeeper is rather slow when it runs for the very first time, because it needs to (very thoroughly) analyze your HD. Afterwards its speed improves tremendously, and once it is trained and running in the background, there is no noticeable load on your PC.
Run the first defrag manually at top priority, as I suggested above. It may take all night perhaps. My disks are 80GB each and Diskeeper (I have V8 for Workstation) always runs in the background. Don't even notice them.
Next time you buy (and fill) such a big disk, start defragging from Day One!