I have owned my E420 for 1.5 years now, and love it. I previously owned 2 BMWs, and consider the build quality of the Mercedes to be superior. No squeaks or rattles on a 10 years old car! The engine is turbine-smooth, the suspension is silky, and fuel economy is better than many V6s. This is a car that I could see myself driving for another 100,000 miles.
Incredible engine - above 3000 rpm it sounds like a race car (but not too loud, as the car drives very quietly). Super high quality interior materials - the interior looks beand new at 10 years old. Not a lot of gadgets to clutter the car (or break - important when you buy an older car).
The only improvements I could offer would be a slightly tighter suspension, but the stock suspension is built for luxury, not sportiness. A slightly higher final drive ratio would make the car even quicker, but fuel economy would suffer.