I still use a 43Gb HD with Workbench 3.1 with no problem at all! Never had a devalidation, nor lost partitions or files.
All you need is SFS for partitions after the 4Gb border and IDEfix97 (from aminet) in order to boot. Oh, and one (never both) of two patches: NSD or TD64 (your choice).
Partitions formatted with FFS must be before the 4Gb barrier, and they can't exceed 2Gb each.
The are after the barrier don't have any limitation if used with SFS or FFS from OS3.5/3.9.
But for better organization and speed, create one partition for each type application: system, applications (work), games, pictures, music and so long.
Read carefully each "readme" on the archives before install and use them!