For many years I have kept my O/S on a small HD and the rest of my junk on other HDs.
All my LAN PCs are running off a 60GB SSD and the games are on the HD, mostly on 320 or 500GB Drives.
My main PC however is :-
C: 60 SSD ( Windaz )
D: 1TB ( Games & Apps )
E: 1TB ( Media )
F: 160GB ( Misc junk )
T: 120GB SSD ( Torrents while downloading )
Having seperate HDs for Windows and other stuff certainly helps for sure, and often by a fair margin too!
Its not only that but I can convert WMV and AVI files into DVD format from E: to D: and also build up the DVD VOBs from D: back into a menued DVD on E: again, as well as burning 4 DVDs all at the same time as playing games and I see no real noticable slowdown at all...
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Even if you only have one large HD, I think that putting Windows onto a smaller partition helps to make your system a tiny bit better in that the disk wont fragment half as much as if you had everythign all in the one basket so to speak, so even before I went multiple HDs I did this and it helped immensely.
For what its worth, even my Laptop runs off one SSD and one HD and I bought an external DVD for if I ever needed to have one... It makes THAT much difference.
And besides, the extra speed you get from an SSD is for me well worth the cost.