Hi, Gary.
4K blocksize makes most efficient use of disk space. If you have a lot of small files that might be a consideration. If you have relatively large files then it won't make much difference.
4K blocksize means twice as many blocks as 8K for the same volume size, which means twice as many FAT entries which means caching the FAT will take more memory. If you are tight on memory or have to support large or many volumes then go with a larger blocksize.
In theory having a block size in accord with typical disk data request size should improve disk performance and optimize cache usage. However nowadays with memory cheap and disk drives with built in chaching that is much less of a consideration, unless you are mirroring slow IDE drives or have a very high rate of disk start i/o's.
Personally, I usually go with 8K.
Jock