My entire effects chain is an MXR M80 into a Big Muff.
When I used to run the Big Muff alone, I usually had one of two things happen:
A: I ran it about the same level as my clean signal (or slightly louder, regardless, at a level that seemed appropriate during sound check), but since it cut out the low end, it made me fall out of the mix when I turned it on.
B: I ran it unreasonably loud compared to my clean. This did the job of keeping me in the mix when I turned it on, but the added volume was just plain absurd for certain applications.
Since I added the MXR, I keep the Big Muff at it's loud setting (B) and use the MXR for a lighter distortion with the clean blended in. With the MXR, I get a very slight volume boost, with some dirtiness on top. It's such an effect that when I'm in a mix with loud guitar, it's very difficult to hear the distortion, but when the guitars cut, it's clear as day. It's an interresting effect if used well, and it can be good to give the music a little extra drive without being ridiculous.
At this point, I hit my Big Muff maybe 3 times in a set, and it's on for maybe 2 minutes total. It's a bit much, at the level I like to run it at, but sometimes my music just needs a squeal of microphonic feedback followed by an obscene burst of pitchless fuzz. It's beautiful.