Monitoring from internal speakers has become addicting, and as such, made the decision for me, as to where I place the mains. If I cannot hear well...nothinhg goes right, so a monitor is paramount. As long as I hear the product, the main speakers can go where they are most effective.
( How DID the Beatles do it??? Especially with all the screaming Must've made for a Hard Day's listening ! )

As for EQ - you have to be aware of changes from room to room. My new Drive Rack PA processor has memory locations that I have set up for different types of rooms and that gives me a starting point that I can work with. For smaller jobs where I use minimal equipment, the Master Graphic in the PRS21k comes in handy. I rarely make adjustments in the course of a performance unless the capacity changes or the volume increases sharply. Mostly, I adjust at the beginning and leave it at that.

The best advice i can give anyone about is EQ this:
Less is better. If you need to adjust, try CUTTING frequencys first. You get the same result from a midrange cut than you do with a high and low end boost. That way the headroom stays high, and the signal is less noisy. Adding highs induces hissssssssss...
Before you make that little smile shape in the graphic EQ....thry bringing the middle sliders DOWN a bit and make the shape that way. It's a better approach that boosting the powerful low end, and the cutting high end. Many sound systems are damaged by improper EQ usage, so be careful. An EQ can ask for up to 15DB MORE of power from an amp, and you may not have that kind of power or headroom to spare. That's where harmful distortion comes in and takes the life out of your mix. Use EQ with great care, and as sparingly as you can to achive the desired result.