Net::OpenSSH looks like a prime candidate. In my original post, I wrote:
I've also looked for similar questions about tunneling in general, and have looked at say, the Tunnels section of the Net::OpenSSH perldoc, but can't wrap my head around how I would create a driver handle that connects over the pipes created by Net::OpenSSH's open_ex method...
So really, I suppose my entire post could have been distilled down to "How do you make DBI connect with DBD::mysql over Net::OpenSSH tunnels?" but I did not want to necessarily dis-avail myself of other possible solutions. I shouldn't have been so quick to dismiss the VPN solution out-of-hand, especially seeing that is, as Salva alluded to above, what Net::OpenSSH's perldoc "Tunnels" section is referring to.
However, these are just wrappers over the sytem-installed ssh and not pure Perl solutions, so if they 'hide the underlying system' enough or not for you remains your decision.
In the absence of any other viable solution, I suppose I may have to settle for something in this approach. The reason I'm hesitant to use wrappers for system binaries is because I'd like to wrap this up in an easily-distributed module to my local team of co-devs, and did I mention the target OS will eventually be Windows?