Depends!
WBFS - works with all loaders, I have had issues with games failing to load (after adding more games to the hard drive) but generally stable, need to use a program to move files from hard drive to hard drive as the format is not recognised by computers.
FAT - only some loaders support it, large files are split (Fat only supports files up to 4GB)
NTFS - write function very poor, GX has issues with the files over 4GB
All however are stable at loading the games.
I use FAT32 as the hard drive can be defragmented, easy to swap files as the computer sees the drive, reliable read and write function