Well, I've only owned two out of the dozens of models they made or make, but my vote would probably have to go toward either the W126, W140, or W202.
I've owned a 202 and now i have a 140...
I think there's going to be a major difference between whether or not you're talking about simple cars (W202) and cars with more bells and whistles (W126, W140) ... the S Class models are just as reliable as a 202 in my opinion, as far as the engine, trans, drive train goes... it's just more electronic gizmos = more possible failures, it's just something you have to put up with.
And to be quite honest, the feeling you have going down the road in a BIG Mercedes (like my 140) is quite different than the feeling of being in a little W202 or something, and so far i feel it's worth it even if you have to put up with a few things going bad here and there, plus it gives you something to do
So generally speaking, there is more engineering that went into cars like the W140 and the W126 because of all the features, and they are excellent cars probably for about the first 5-10 years but as we all know, age causes things to go bad. My W140 needs a few minor gizmos fixed but nothing that affects the drivability so it's not a big deal, after 113k miles my engine and trans run superb, although I think the trans may just need an adjustment, as far as shift timing goes, etc.. of course my W202 needed that as well, I guess they get outta whack after a while.
But, regular maintenance, in fact "over maintaining" is what I would recommend, do things before they even need to be done, flush the trans every 50-70k miles, replace the fuel filter every 50-70k, etc etc.. helps the car run nice.
In short, I guess I'd have to go with a W140.. I heard quite a few horror stories about the W220 and the W221 is too new to really know... JD Power rates MB pretty high these days though, so things are looking good!