The data reduction (dedup and compression) is inline so practically it makes no difference. I'd present it to vSphere as normal, create a datastore(s) and put your vm's drives on it/them.

There's no benefit in messing around with RDM's, or in-guest iscsi.

Right, As Brett mentioned it doesn't matter how you present the LUN to host, In Simple terms, This Data Duplication happens once the host writes reaches the XtremIO device but not at Host level which is writing the data, So with that said XtremIO doesn't care which type of host(Windows VM or ESX server) is writing the data to the XIO LUN, You can present the LUN in any of your preference.

Don't forget to look into sdelete/dd to make sure you get the most "thin" benefits possible. Also think about how that translates to VMs (some versions of ESXi support UNMAP , some require manual intervention).