Usually just guitar > amp. Simplicity is good.

I use tube amps, and set up so that with the guitar volume turned down, the amp is just on the edge of distortion. When I want grind, I dial it from the guitar.

If I want pedal distortion, I use a Bad Monkey. The tone controls are good enough that I don't need additional EQ. And I have an old Dunlop JH-1 wah that sees very little use.

I used to get all tangled up in massive effects chains but I found that the tone really suffered. If I want spacy effects, they get added in recording. Playing live is a different game altogether.