I'm strongly considering a new daily driver. The C55 that fills the role now is an absolute riot to drive but it's a bit tight for my 50 year old 6' 230 lb frame.
Before we get into the cars, a quick bit about me. I'm a hot rodder, machinist, fabricator, and gunsmith with my daytime job being a parts guy at a non-MB dealer. My other vehicles are a 1992 Dodge D250 Cummins truck and a 1972 Chrysler Imperial with a 541 cubic inch (8.9 liter) V8. The Imperial and truck are the same length, each being nearly 2 feet longer than a W221.
My experience and familiarity with MB vehicles is extensive. I spent 15 years working the parts counter at Mercedes stores, was Master certified, and my training transcript holds more than 180 entries. I have no problem doing my own maintenance and repair. For things I'm not set up to do, I have good friends in the MB world and still get a significant discount on parts. My commute to work is about 20 minutes these days but I tend to drive quite a bit. In fact, I've had my truck in 37 states. It didn't get 337,000 miles by sitting in the driveway.

Current daily C55 pros:
Rock solid reliability.
Fun to drive.
Not bad on gas (16 city 22 highway).
Dirty cheap to own.

Cons:
A bit cramped inside.
Gets claustrophobic on a road trip.
Not enough power.
Near zero aftermarket support.
Drags the front bumper on everything in sight.

If I replace my C55 it will be with another AMG. I'm currently looking at a 2011+ S63, 2012+ E63, and 2012+ ML63. All can be had for similar money.

The contenders:
The ML63 has the nicest seating position (I prefer fairly upright, not slammed back like a 2 dollar hooker showing her goods) and best visibility. It's the lowest performer by far and the side steps stick out enough to be in the way but not far enough to be useful. Brakes, unlike the other two, are pretty cheap. Airmatic can pose issues but they're fairly solid in the long run. Features and options are on par with the 212 but fall well behind the 221. MPG is the worst of the bunch. Light towing is possible, it'll have room for hauling stuff, and I'll never drag the bumper again!

E63 is where the performance is found. Silly fast in stock form, they get crazy fast with a tune. Seating position is not bad but the top of the door trim panel is a bit awkward for someone like me who rests his arm up there. Brakes are nearly as expensive as the S-class. A downgrade to C63 brakes is possible to save money. Reliability is average since the car is lacking many of the features that make a 221 special. MPG is the best of this bunch but not by a significant margin. Trunk space is up slightly from the 203. AWD is available and decreases the brake rotor cost but increases the opportunity for driveline failure. Bumper dragging is to be expected.

S63 is a very nice place to be. It's a lumbering beast compared to the C55 and even the E63 but not too bad in the grand scheme of things. Comfort is very high, assuming the pneumatic seats are working. If I go this route it will be equipped with the rear seat package and night view assist. Because I can. Cost of ownership is very high. Replace an ABC pump lately? Highway cruising is hard to beat and it's not bad around town. A bit less maneuverable than the others when it comes to tight spots but still demands far less acreage than the Imperial or truck. This car has the most going for it which means it's also got the highest chance of failure and resulting high cost of ownership. Even more if I get silly and splurge for an S65. The trunk space is quite nice. Yes, you can poke the button to raise the car over parking curbs, but let's face it, I'm going to end up dragging the bumper car too often.

Now, your job is to make the case as to why I need the ML63 more than the other two vehicles.

 

You don't! E63 would be a better choice for you since most importantly it fixes all the C55 cons you mentioned while retaining (at least) one of C55' pros.

 

Stay away from any ABC equipped MB. They are money pits. You would love the ML63 bi-turbo.

 

Tuned ML550 or ML63

 

I can't speak to the 63 engines but the W166 is a solid chassis. No concerns.

I don't care for the E-Class. It's not comfort-oriented enough like the S-Class and in AMG form would be very uncomfortable for me. If a sports car was needed I would go with C63.

For me it would be S63 or ML63. I've been a truck and SUV guy forever, so ML63 for me because of the space. S63 is a great concept but I load the vehicle with junk and take it off road every now and then, and I wouldn't feel good about doing that with an S-Class. If your only driving is to Costco and long haul road trips, S63.

 

I have a 14 ML63 and love it. Mine has the 21" wheel option so the ride is a bit more rough than intended on an SUV but it achieves the sporty look that way in comparison to a non AMG version or just a sport package ML. If you were to go the ML route I believe try to go with at least a late MY13 build assuming it gets the updated timing chain and timing components from the factory. The initial M157 engines had a slight chain stretch issue due to the link types in the timing chain.

I too was looking at an S63 or E63 initially, but then came across my ML63 and it gave me versatility to use it as an all around car and not needing dedicated winter tires. I've taken advantage of the folding 2nd row plenty of times to pick up larger boxes that would not normally fit in a traditional sedan trunk.

I feel the performance sedans get all the spotlight on YouTube and other automotive avenues because of their design and flagship (C32, C55, E55, E63, S55, S63, S65, etc) but I would definitely hope to keep my ML63 for as long as I can. I was able to pick mine up nearly fully loaded (no night vision, bang and Olufsen, or rear entertainment) with about 33,000 miles on it. I've put on 12,000 miles since then - so I guess you can say I like it. I've actually averaged about 15.2 MPG as well and I'm really not mindful of trying to achieve high MPG - but I also am not really heavy footed and ragging on the car. I'll do a pull every now and then on an expressway to remind myself what I'm in.

 

Might I suggest an E63 wagon?

Also, the S550 coupe.

both bigger and will move you, while being sedan (vs. suv) based.

long haulers both.

 

You came pretty close.

I wanted to thank you folks for the comments. I made a purchase and will be picking up my 2013 CL65 in the morning.