Different drive letters will work without performance concerns. An alternative (only necessary once you exhaust drive letters) are mount points. To create a mount point, create an empty folder on any existing NTFS volume and then use the Disk Management mmc to mount the disk volume in that empty folder instead of assigning a drive letter. Repeat for each drive. See mount a drive in a folder for detailed instructions.
Below is an example of what the directory structure might look with all mount points on drive M: folders.
M:\MountPoint_Disk1
M:\MountPoint_Disk2
M:\MountPoint_Disk3
M:\MountPoint_Disk4
...