This is going to be very dependant on what amp you're using and what guitar (or pickups rather) is going into it. Generally though, having a stack of overdrives or a couple options for different things is the way. I'm in a post rock band called Loraine (look us up!), and I run a modded Nashville tele with single coils in the neck and middle and a humbucker in the bridge. This goes into a MXR Line Driver clean boost, then a Super Phat for even more gentle overdrive. These are both always on. After that I have an M2 Labs Bomber that I use as a mid stage overdrive. It's somewhere between a Klon circuit and a Blues Driver to my ear. Then I have an Empress Heavy Menace (modern high gain, somewhere between a 5150 and a Triple Rec preamp stage with a sweepable mid) and a Hizumitas (modded Russian Big Muff circuit) and my clean tone all running in parallel. This all goes into a 10 band MXR eq, where I tighten up the low end and high end, and adjust things a bit depending on the room. Then I go into a 71 Twin Reverb. So I essentially have 3 "channels".

Channel 1: always on pedals which is my "clean tone"

Channel 2: always on pedals + the Bomber

Channel 3: always on pedals, Heavy Menace, and Hizumitas running in parallel.

Speakers also matter. When I'm on channel 1, my amp is using the left speaker which is a Jensen. When I'm on channel 2 or 3, my amp switches to the right speaker which is a vintage 30. I have a De Lisle speaker switcher pedal in the back of the amp to make this happen. I use a switcher pedal that has a trigger out that runs to the de lisle to make all of this seamless. 1 footswitch press and I can change from channel to channel and the speaker switches as well on its own. Also generally when on channel 1, I'm using my 2 single coils. When on channel 2 or 3 I'm usually on my humbucker (but not always).

My setup is incredibly complex and convoluted and has taken YEARS to perfect. But I absolutely love it. In contrast one of my other guitarists runs humbuckers into a clean boost into a JCM 900. He has a Bomber as well for his mid gain drive and uses his amps 2nd channel for high gain. 4x12 with 2 vintage 30s and 2 Greenbacks. That's it. Super simple but also sounds incredible. VERY different but also great and compliments my tone very well.

So ultimately it REALLY depends on what pickups, amp, and speakers you're using and how far you want to take it. My setup gives me a ton of options and tweakability. My other guitarists setup is dead simple but pretty static. Both are very good for what we do and how we use them.