It all comes down to personal taste, of course. But I tend to keep the tone controls around noon (e.g. bass 4, mid 5, treble 6 and presence 6). I also go easy on the gain and use a klon or timmy for gain boost. For my 'fatter' JCM800 Marshall sound, I ended up using the 412 Greenback 20 cab with the 121 mic (5" away, lo cut at 80, hi cut at 10kHz) and the Matchless H30 with the 409 mic (lo cut at 90, hi cut at 6 kHz). The master volume parameter is at 8 as higher settings muddy the tone).
Marshalls are made to scream, but I use the above as a basis for my crunchy, mellow lead sound. I also play a lot with my fingers and that mellows the tone too.