I would screw it in if you can at all. If the 3.5 inch bays are open at the bottom, try to bend them out just a tad to make it fit. If you can't, then whatever, but if you can, do it. Harddrives vibrate when they're spinning, and that could cause it to shake loose and fall, which could break the drive (basically what Prophet said). ANother thing to remember, if it's one of the drives that can take both the SATA-specific power plug AND the older types of plug, ONLY USE ONE TYPE!!! DO NOT PLUG THE DRIVE IN TO TWO POWER PLUGS AT ONCE!!! Otherwise, it's pretty much plug in, boot to windows, and format. Format it NTFS on one partition. The only Partition/performance relation I ever heard about was installing Windows on a partition about 6-10 gigs large for Virtual Memory, and putting all your other files on another drive. But if you've got a 500gig drive, that shouldn't be an issue.
Any problems, I'm your guy. Do you know how to partition/format a drive while in Windows?