If we talking back in the day I always preferred the HoneyBee SG6, apparently known as Competition Pro in the States. I still have a couple, they just had a much more "dpad" feeling...dpad.
Even when the system was out Sega couldn't make the best controllers
When I originally got my Genesis Model 2 in the early 90s, I had the big 3-button controllers and clocked most of my time on that. Out of the original releases, I have to go with that version. The bigger controller felt very comfortable to me.
Later on I had a Model 3 as well, and didn't care much for that version of the six button controller. It felt a little too small in my hands. Also, both of the six button controllers I got around the time of the Model 3 eventually stopped working.
I had been looking for a solution to my Genesis controller problem and tried out the 8bitdo 2.4g six button, which I purchased in 2020. I haven't looked back since. The controller feels great and is very responsive, so that's my go to nowadays.
I like them both, for the many reasons that have already been stated.
The three button controller has a better dpad. The six button, depending on the variant, has a spongier dpad. But overall, having six buttons is preferable. It still seems like a miss that there weren't L & R buttons. And three buttons is still questionable.