Will PFS-2 work with removable media like Zip and SyQuest drives ?
Yes.
Fourth Level Development had special removable media support tools which they bundled with their drives. The packages were also available separately. Without this software, you have to do the same thing you would with FFS on removable media -- HDToolBox, etc.
It is suggested that you partition all your cartridges the same. The Amiga reads the RDB, partition table, at boot time only. You should also leave a disk in the drive when you boot.