So I am trying to figure out what might be causing a very slight "whooshing" sound that appears to be coming from the A/C vent to the left of the steering wheel on my wife's 2000 e320 wagon. It's barely audible. Someone suggested that it might be a leak in the vacuum accumulator translating through the HVAC system. I hope not. Has anyone had this issue before or know what it might be?

Try playing with the vent position control to see if you can find a correlation. There's also the flap test program that you can run. I can find the instructions for that if need be; they're in the FSM.

It's not a hiss, right? A hiss could be due to low refrigerant or a restriction.

From your description it sounds like the A/C system may be slightly under-charged. What you're hearing (if I'm right) is the expansion valve opening and closing. Try pushing the "EC" button and see if the noise goes away. If it does, top off the system.