Capacity, mainly. The 450Vx doubles the storage to 4 TB and is sized for around 600 mailboxes instead of 300. Deployment options, licensing, and the core search and compliance features are identical between the two.

Yes. It's built to be email agnostic, so it can pull from Exchange, Office 365, Google Workspace, GroupWise, and Lotus Notes at the same time, which matters if your company never fully standardized on one mail system.

It can run alongside other virtual machines on the same host, as long as the host has enough CPU, memory, and disk to spare. For an appliance handling continuous archiving for 600 mailboxes, most customers still give it dedicated resources rather than letting it compete for capacity during busy periods.

Yes. Barracuda Cloud mirroring is an option, not a requirement. You can just as easily mirror volumes to your own external storage over the network if you'd rather keep everything inside infrastructure you already control.

Per appliance. One subscription covers the 450Vx regardless of how many of your 600 recommended users you're actually archiving, with no per-mailbox fees added on top.