I suggest you cerate more than one store in the storeonce software store. Usually Stores are created for different backup types. so you would create one store for Exchange DB Backup, one store for SQL DB Backup, one store for File Backup Windows, one store for file Backup Linux. I would not configure to much stores, because best performance with one store. (white paper)
Please keep in mind the max recommended size for storeonce software store ist 20TB. I dont know how big your environment is, maybe it would be better to use a hardware box...
Regarding our experience, we started with Software StoreOnce almost 2 years ago. Lots of problems then, lots of debugging (we proudly feel that some of the published fixes were ment for us) but last 4-5 months have been calm (but we're still cautious regarding stoping a Store).
We use RHEL 6 only. Some physical, some virtual, almost the same. We use one store only in each StoreOnce system and 1 for each kind of data (File System, MS SQL, VMware, Exchange). Ratios get bether this way.
We keep stores small but that depends on your usage: we don't use give more than 6 TB to a Store.
We tried Windows but performance seemed worst, specially when housekeeping occurs (but as I said, we had lots of problems when we started).
We use ext4 with LVM but we always suspected that XFS would be better.
We are now testing StoreOnce Virtual Store Appliance. Very good! It uses RHEL 5, IBRIX (instead of LVM) and XFS (instead of ext4). Performance is very good, we are considering changing to it (better support, better management, more features like when copying an object from one VSA to another not beeing rehydrated).