You may be dealing with the problem that the OS itself (or its apps) like to randomly read stuff off every hard drive when it's bored. At one point I tracked my OS's disk access activity, and sure enough, Finder banged another external drive about every 5-10 minutes in round robin. This was 10.5 so maybe they fixed this.
Some programs also scan all your drives looking for resources, and once they find it on an external drive, they will continue looking there forever, even if you delete the folder. I suppose you could rename the external drive. For instance, my system believed that 3 of my fonts were located on external drives, so everytime I opened a Font menu, I would get a beachball for 10 seconds while the drive spun up. I was able to mess around in Font Book and make it stop doing that. Same thing when I start Word, which apparently has a prurient interest in "Word Settings" folders on my backup drives.
You can see what files it's getting on external drives by doing (at Terminal)
sudo fs_usage -f filesys | grep /Volumes/ and then it'll pop up everytime something goes to an external drive.
Note that this is a considerable resource-hog, so I don't run it when I am not actively using it.
To this day, everytime I go to an "open" or "save as..." menu, again, beachball for 20 seconds as every drive spins up one at a time. I don't think there's a way around that one.
These are commonplace external hard drives bought at CostCo, not some gold-plated "designed for Mac" specialty product. They do indeed spin down when nobody is using them.
I have chased my tail for YEARS on this problem, for instance I finally got the Fonts problem resolved (I think), but every problem I solve, two more pop up. I have just given up, and everytime I get a beachball I throw another dollar into the "buy solid state drives" fund.