The EICAS message/alert might be the way to go but a couple of observations:
1. Are you going to have the alert displayed every time you deliberately go off 121.5 to get ATIS or talk to company et.al (Yes, I know on some types there's the luxury of having 3 VHF Boxes,but it seems some types don't).
2. Will an alert be triggered, if, say, VHR X has 121.5 as the active freq, , the crew have correct audio selected on the ACP but volume(s) is/are turned down.