Not sure what you mean by set them up but I have a 74gig Raptor and a 400G Seagate so I'll tell you how I fill them.
The way I do it is I have my OS installed on my Raptor, along with all the games that I play frequently and therefore IMO need to be able to load faster (Steam games, BF2/2142, C&C3).
I have my My Documents folder redirected to my 400Gb drive, where I keep all my music files, video's, ISO's, games that I usually only play at LANS or not very often and all that other stuff.
I keep a pair of backup images of my 74Gb Raptor on the 400Gb drive which I update every few months.
I'm looking to buy either a Second 400Gb to mirror my 400Gb drive or buy and external HDD soon so that I can back up my 400Gb as well.
Neither of my drives are over 50% full and I defrag frequently.