In my experience, it usually is.
When a program is installed, it makes a few entries in a file of its own, and it is different for every program. Some of those files are accessible, some are not.
Also, during the installation process, not all files are installed in the destination directory. Some files are copied to \Windows\system, some files are copied to \Windows and some are copied to other program directories under \Program Files.
And I won't even bring up the registry...
In short, it's just not possible to easily move a program from one drive to another. (unless it's a simple game!)
So the best way to setup a system like that, is to create a partition for the OS (drive C), a partition for the programs, and another for a backup of drive C.
Backup often. You can also backup on CD-R or CD-RW, as an alternative.
I like to create another partition for data, the actual files that I'm working with, just because it's easier and simpler to backup all of it. Most of the times, I just tell people to keep everything under one folder, like "My Documents" (with whatever directory structure they want).
When you create a partition for the OS, make sure you leave enough room for the swap file...
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