As some already noticed; when creating a snapshot on a VM with two disks the block size of the VMFS volume which hold the working directory is checked before the snapshot is taken. As reported by VMTN User Pizang this was not the case in ESX 3.x. You can imagine that this can cause issues when the second disk of a VM is larger than the maximum file size dictated by the block size of the VMFS file system which holds the working directory of the VM. What? Yeah I had to read that sentence at least 3 times before I understood what I said… This might make it easier:
Disk01 – 10GB stored on VMFS001 with a 1MB Block size
Disk02 – 350GB stored on VMFS002 with a 4MB Block size
VMFS001 contains the working directory of the vm “virtualmachine001″. Snapshots are stored in the working directory. In the case of Disk02 this could mean that the delta file grows beyond the maximum file limit of 256GB of VMFS001 where it will be stored.
Another example of where the block size could limit you is outlined in this KB article: http://kb.vmware.com/kb/1012384.