My girlfriend has a 400E - it gets 17-18 in a suburban environment and will return 22-23 MPG on the open road. The car has a 2.24 rear whcih really helps things on the highway.
I'm amazed that a car with so much power on tap is capable of getting low 20 MPG numbers on the highway.
I agree wih a previous poster about winter mileage -its quite a bit worse. Turning on the A/C also seems to hurt mileage much more than I would expect.