Although the new generation S-Class (W221) seems to be vastly improved over the prior (W220) version, it's nonetheless a plethora of computers, sensors and other electronic components. If this were 25 years ago and the same question about "long term" involved a 6.3 or a 6.9 vs a 4.5, I would be comfortable recommending the more "exotic" variations of the W116 and W126. Today, the repairs aren't about shocks and wheel bearings but more about air suspension systems that cost thousands of dollars to fix.

The S600 is a great car, but in this scenario, it's just not the winner in the "long term" contest. Owning one "out of warranty" could be a very hairy experience.