Thanks for the suggestions - I'll need to do some more experimentation when I get back in the office, but I think you're on to something, perhaps with the router at Location B in my examples. I did a straight UDP speed test with iperf3, and that worked fine - over 500Mbit/sec - there shouldn't be anything funny with MTU going on, nor any IPv6... however I did two additional tests:
At my main location, I've got another "low end" box on the same local network as the "server" - this one is an intel Atom CPU - with that I was able to get about 585Mbit/sec (compared to the 930-940 without wireguard).
I've got a 3rd location available - actually a low end VM on AWS - this one gets around 300Mbit unencrypted, and actually tested above that via wireguard - I assume thats just normal fluctuation, but seems to point the finger to something specific at location B, my office. I'll continue to investigate and update if I figure anything out... it'll probably be at least a week before I get anywhere though, due to work travel.
Thanks again,
Scott