So thats what MacFUSE is for...
Is it easy to set up? Or am I going to run into lots of complications?
Most external drives I've seen are pre-formatted as FAT32.
For maximum compatibility, zero configuration, leave the drive as FAT32. Both the Mac and PC will be able to read/write w/o doing anything special.
If the drive is both FW and USB, and your PC lacks FW ports, no problem, connect it via USB on the PC and FW on the Mac.
Using HFS or UFS will make the drive unreadable by the PC.
The only benefit of using NTFS: it the drive is stolen, another PC will be able to read the drive, but the PC user will not have permissions to access the data. Even so, any Mac will be able to read from, but not write to, the drive without 3rd party software.
In short:
Fat32: no issues, plug it in, it works.
HFS/UFS: Can't be read by the PC without 3rd party software
NTFS: Secure, but cannot be written to by the Mac without 3rd party software.