I can speak intelligently on this, I've owned a 2020 E63S so pre-lci, traded it in with 25k miles for my 22 M5 which I'm at around 1700 miles now.
In general the differences are very nuanced between the cars. Both are absolute beasts, wolves in sheep's clothing. Fairly sleeper cars, I've had the rear debadged on both and live in a smaller town. I feel like the E63S is less known and is always underestimated compared to M5 by general car guy public so to say.
Biggest thing which is no surprise is that the M5C is more refined, there is very little drama and theater when going WOT, quieter cabin, smoother shifts and quieter exhaust hide the sense of speed and acceleration in comparison with the AMG. The E63S was very bipolar, the throttle response was too limp in comfort mode so when you put in Sport+/Race its felt like it wanted to rip faces off, just an angry monster hiding under the hood. The M5C comfort mode is sporty in comparison, which is much better for regular daily driving, BUT it what makes going into Sport+ mode less dramatic.
Exhaust note: with ALL the valves open the E63S wins this round, its an absolute angry animal, its loud enough that you forget its factory, so much so that I've never even considered an aftermarket exhaust, its just loud enough where more would be too much. It doesn't fart or burble, it BANGS at right RPMs, when you let off at 4200 rpm its always random BANGS. Yes I know its programmed like the M5C, but in the BMW the burbles are way too uniform, its too synthetic in comparison while the BANGS in the AMG felt natural. I've noticed sometimes the M5 does bang at very random times but very rarely and its hard to recreate. The fart as I like to call it between shifts in the M5 does sound good when its bounced off other cars. In the AMG you could open/close 2 of the valves with a button, the 3rd valve would only open during Sport+/Race modes akin to M5 valves.
Now some maybe be surprised, but when idling or during start up the M5C exhaust is louder, it has a lot of BASS if that make sense, that low tone noise. The M5 does bark on WARM start ups way more aggressively, in fact on warm start ups the AMG lacked that bark. There is a function in the AMG called "emotion start", its when you push the start button and hold the "-" paddle down immediately, it would rev up to a higher rpm, but you gotta hold it down each time and sometimes revving up to a higher rpm you heard the engine belts whine more than the exhaust (like if you press the pedal during idling to 2k rpm). On cold starts both sound good to me, AMG did sound more muscle car like, more growl, like a chevy small block, especially in the winter months cold starts. In comfort mode the AMG like the M5 is pretty quiet you hardly hear anything and its a pretty civilized sedan, you can drive it like that for weeks and forget there is an angry creature under the hood, which even during 2 years of ownership could surprise you.
The M5 shifts much smoother and much faster, I might be wrong but I think the MCT in the AMG does have harder shifts for more drama but not as quick.
Since it was Pre facelift 2020, the ride was very harsh, lots of cabin noise, they fixed it in the facelift models like they did with the M5, but M5 is a dream compared to the E63S. I thought the E63S would vibrate itself to death, it was so harsh, unless you live in Florida with that smooth asphalt, on more rocky type asphalt you can feel the vibrations. I had all season tires which helped, but my M5 with P zero rides much smoother and quieter.
Neither car feels faster than the other, yes you don't SENSE the speed as much in the M5, but being thrown back into the seat and dominating traffic feels the same in both cars. Yes I know the M5 is faster as proven by many comparisons. My E63 did have the Renntech ECU tune, but rumor is that the computer after a few weeks limits the power back to stock, which might be true as the car did feel "slower" after a while. Even with that in no way shape or form does the M5 feel slower, in fact it feels more responsive, faster kick down even in comfort mode.
Interior was definitely more elegant and prettier in the AMG, it had a little classic style IWC clock on the inside, more areas with carbon fiber, aluminum buttons for climate control and NO PIANO BLACK PLASTIC!!! Cheap plastic on the steering wheel airbag though. Having said that the LCI M5 interior is in no way worse, its more sportier and more utilitarian I'd say, it FEELS like better quality, mainly because the ride is not so jarring. Both cars are pleasure to be in, the piano black plastic pieces suck, collect dust almost immediately, plastic buttons instead of aluminum, but leather on the steering wheel and in general the leather and seats are slightly better. And BMWs UI is leaps and bounds better, just in general best UI of any car I've used.
Both cars have the "basic" sound system, and the AMGs Burmeister is a tad better than the H/K in the BMW, this is playing music over a USB from an MP3 player, which is how you get quality sound. Radio or any streaming music is the same in both.
E63S had cylinder deactivation and coasting mode, so I got 26mpg on a road trip once, in the city it would be 16-18mpgs.
The multibeam LED headlights were better in the AMG, cool transition between low and high beams, cool pattern when starting it up at night, and light density was much better, much clearer and whiter light. Can't speak for BMW lasers as my car has the regular LEDs, they just seems like any other LEDs no different than my GX460 LEDs, the AMG were noticeably fancier.
AMG had 67 shades of interior lighting, which was gimmicky as I've only used 2 or 3 throughout the 2 years. I like the simplicity in the BMW more. The ventilated and massaging seats were also a gimmick, so I didn't even optioned them out in the M5. Never used self driving cruise control or self park.
Some info gauges are better in the AMG, there was one that showed you both the engine and transmission oil temps, to note the tranny temps take longer to get into operating temps, so I wish M5 would have it, because the oil temp gauge is misleading, after a cold start when it shows normal op temp I guarantee the tranny oil is still not there yet.
In the E63S you need to hold the trunk switch up to open the trunk, in the BMW you hold it down lol. Both cars wireless phone charger won't fit your phone, my S21 would fit without its case barely in the BMW, but its always in the case. The E63S albeit a 2020 model didn't have any USB-C ports, didn't have rear climate control, while its standard (4 zone) in the M5C. The sunglass holder in the AMG was made for kids sunglasses or something, unless you wear aviators that fold completely flat, nothing would fit in there, useless.
You can switch your driving modes and especially your chassi/suspension setting by buttons on the fly, without going into the menus. The E63S has a slippery mode which is basically are even more limpier engine mode after comfort. The steering was a little more precise, but its not really that noticeable at least to me.
Lastly if you have the opportunity to own both cars you won't be disappointed with neither, both are amazing hyper sedans. The things I miss about my E63S are very small and inconsequential, the M5 puts a smile on my face and in my heart just the same if not more. Some reviewers claim M5 lacks character, I disagree, it has different character of its own and is one of the best sedans ever made. It be interesting to hear someone go from an M5 into E63S, LCI, too bad the E63S are extremely hard to find since they cancelled the 2022 models.
