The VMFS Datastore block size does not affect IO size or performance, it only affects the allocation sizes in the filesystem for individual files. An 8MB block size essentially means 8MB is the smallest file size. Since VMDKs are generally GBs in size a large block size is not an issue. If you think you may have VMDKs approaching 300GB in size then you will want to go with larger block sizes. There is really no downside to a larger size.

Richard Anderson

When chosing your block size, keep in mind that to take advantage of VAAI (vStorage APIs for Array Integration) and the array hardware acceleration primitives such as "Full Copy" (cloning, Storage vMotion, etc) which copy between datastores, the block size must be the same.  Otherwise, you lose the offload to the array and, of course, simply reverts back to the way it was without VAAI support.

Since VAAI requires FLARE 30 and vSphere 4.1 (as well as other several other configuration settings such as using ALUA for the Navisphere/Unisphere host failover mode), this might be something to look forward to and plan for now.  Therefore, I'm simply bringing this up as (a reminder) you may want to standardize on one value.

Many people (scattered comments on Chad Sakac's blog) choose 8MB in consideration of standarizing and the flexibility of the larger file/datastore sizes.  As already pointed out performance is not usually impacted and generally not too much space is wasted either with the larger block size.