Having separate partitions and/or multiple hard drives has proven itself to me to be all positive and I recommend it highly.
One of the things that I do with my systems is to create a folder on a separate partition or hard drive and name it "My Documents". Windows loves to put things in this folder, and I've found that it can be convenient. However, it grows quickly with videos and pictures, etc. and will soon be "cock-roaching" real estate better suited for the Operating System. So let's move it off of this C drive partition.
Right click the My Documents folder in your Start Menu which is on your "C drive" and choose Properties.
Now, change the Target to the new "My Documents" that you created on the other partition and transfer all the items to it. This will clean up a lot of space on the C drive and insure that the items stored in that folder are not lost should the OS need to be reinstalled.
Creating another partition for Programs is a good idea as well. If the C drive does need to be wiped and the OS reinstalled, some, if not all of the programs, on the separate partition will still work with out problems. Any that do balk, just reinstall them into the same folder on the same separate partition.
My personnal feeling is to leave an Anti-Virus program and any Firewall program installed on the C drive. These programs work tightly with the OS and I found that it's better to keep them close.
Create a partition for Games if you're a gammer.
Another one that I create is for Downloads and Music.
As mentioned, this keeps much of your data, pictures, etc. safe, should the C drive become corrupt, infected or need to be reinstalled. With multiple partitions, multiple operating systems can be installed and used as well.
Smaller partitions also defrag alot quicker............just an added bonus.