It is indeed possible - many people use such a setup so that one drive can be used for both WBFS/USB loading and homebrew (Mplayer, etc).
You can partition your drive on Windows XP using third-party software like PartitionMagic, or using built-in functionality on Vista or a Mac.
Note that the order the partitions were made is important - if you want to use part of your drive for MPlayer, that partition MUST be first in order on the disk; if you already have movies and shows on your drive, you can leave them there and make a new partition that comes after. The WBFS partition can be anywhere on the disk, but MPlayer and most homebrew apps can only read the first partition.
To partition, make sure you have ~220 GB of free space. Defragment your drive. Shrink and partition your drive to make the new partition by 200 GB, format it as FAT, and then format it with a WBFS manager.