Pres CTRL+ALT+DEL again. Now click the Processes tab. You see all that stuff? All those processes are running. Applications tab might be empty, but that's only for programs you manually start. There can be 100+ processes working in the background.
Also when that happens, click the Performance tab. You can see CPU usage and Page file usage there, plus some additional stats. Do you see anything special regarding these percentages when your disk works like you have described?
What else? Virtual memory file. It's better if you set it to a constant size, at least 1.5× the RAM size you have. I know for sure that some of that HD work comes from changing size of the swap file that virtual memory uses. If it's constant size, there is no changing size.
Check the fragmentation of the drive. Defragmentation of the drive can literally makes you sit there, not believing how much smoother everything works.