This has proven to be a rather sticky problem.
I sorted out a minor wiring error, replaced all of the FTDI SMD chips on the breakout boards, and.. over the weekend managed to fry all three of them AGAIN, and even fried one a third time after replacing the replaced chip again.

They work, sometimes, then die mysteriously. One thing they definitely don't like is sharing the ethernet cable with ethernet (2 pairs for serial, 2 for ethernet). Instant death doing that. The last one fried while operating on a dedicated run of cat5e not shared with anything.

So.. more FTDI replacement chips are on the way from digikey again .. the FedEx dude ought to be here around 11am Tuesday with them. And this time I'm putting a dedicated serial adapter inside the thermostat itself, and running the USB back to my PC over cat5 with a pair of DX.COM USB extenders.

That ought to put an end to frying the serial adapters.
Next up after that is taking over the HRV air-exchanger controls.