After a couple weeks of troubleshooting by EMC/XtremIO and VMware engineers, the issue was determined to be an issue with EFI boot handing off a 7MB block to the XtremIO array, which filled the queue, and which would never clear as it was waiting for more data to be able to complete communication (i.e. deadlock). This seems to only happen with EFI firmware VMs (tested with Windows 2012 and Windows 2012 R2) and the issue is on the XtremIO end.
The good news is that the problem can be mitigated by adjusting the Disk.DiskMaxIOSize setting on each ESXi host from the default 32MB (32768) to 4MB (4096). You can find this in vCenter > Host > Configuration > Advanced Settings (bottom one) > Disk > Disk.DiskMaxIOSize. The XtremIO team is working on a permanent fix in the meantime, and the workaround can be implemented hot with no impact to active operations (potentially minor host CPU load increase as ESXi breaks down >4MB I/O into 4MB chunks).