Hardly.

The system drive (very usually C:/) is where the Users folder lies by default (and you can’t move it anyway IIRC), folder that contains stuff like the Appdata folder where… well… apps keeps their data like settings, history, backups… Most software will try to access it and would meet an “access denied” error.

This is also the default location for all the documents, music, videos, pictures,[…] folders (but you can change those though)

Basicaly you’d be limited to the “portable” versions of softwares located on other drives, which is not quite the norm on Windows.