First, there's no right or wrong way to set things up. It really all comes down to what you prefer. And it may take a few weeks to discover what works best for you.
I often tell new tablet users to put their mouse away for a week and use only the tablet for everything. This helps acclimate you to the stylus when you've been accustomed to a mouse.
What follows are merely my preferences. I use 3 monitors and currently have an "large" intuos tablet. I am also right-handed so, clearly, your set up may need to be altered for left-handed use.
I set my tablet at an angle off to the right, kind of where a mousepad would be. The keyboard is slightly off-center to the left, but not much.
I use my tablet as my only input device and have it mapped across all 3 screens. I literally haven't touched a mouse in years other than to install an OS and then the subsequent tablet drivers.
I know many users feel there's no benefit to a tablet unless you're drawing/painting. I would disagree. I can work for hours on end with absolutely no hand cramping issues or fatigue due to pushing around a "soap on a rope". If you've ever pulled an all-nighter with a mouse, by morning your fingers and hand just feel tense. That's not the case with a stylus. At least not ever for me.
Many (many) years ago I actually saw a doctor about a big lump on the back of my right hand. It was painful and sore with any shoulder, arm, wrist, hand movement. Turns out it was what he referred to as a "ganglion". A ball of nerves that have essentially seized up due to strain. This was entirely due to using a mouse too much. I'm not saying that'll happen to anyone else. However, I had to learn to stretch the arm, wrist, hand, more if using a mouse for long periods of time. Since getting a tablet, that's never even been a slight or remote issue.
Using the stylus is just more natural to me than any other input device and I don't know why I'd ever want to use an inferior device just because it's seen as "standard". So for everything -- Illustrator, Indesign, Photoshop, Mail, Browsers, Finder -- I use my tablet as an input device.
The only issue I have with this maybe the drivers. Sometimes Wacom drivers aren't the best. They used to always be perfect, but in recent years the drivers have created some headaches. So I suggest always retaining old driver files. It's often been the case the past few years where I've needed to revert to older drivers to overcome some horrendous bug in a new driver.
As for the buttons, I'm not very big on using the buttons on the tablet. I'll use the radial touch input for tracking videos as a scrub wheel, but other than that I really don't use the tablet buttons. But that's my preference. I've never been one to use only the tablet. I've always had the keyboard close so it's never been imperative to me to move as many functions to the tablet as I can. Some users prefer to put the tablet dead center in front of them and move the keyboard out of the way. I simply swivel to the right a bit if I need to.
The stylus toggle button I have set the same across almost all applications. I set the bottom to be Command and the top to be Control (Mac user - I'd set the top toggle to Right-click on a 'Doze system). These are often the two most used things on the keyboard for me.
- For most Adobe apps, I set the toggle to Command and Option, rather than control.
- For Photoshop, specifically, I set the bottom toggle to be "pressure hold" rather than command.
- And I set the top toggle to be "check mail" for my mail client.
But other than that I leave them at command and control.
I'm a big believer in consistency breeding faster work. The less I have to think about where a panel is or what a button does, the less I focus on how to do something and the more I can devote to what I'm doing. So I try and keep the input to the applications relatively consistent - all panels on the right monitor, and tablet buttons the same for the most part.
Other items - Never used a scroll wheel so I don't miss it. The spacebar on the Mac scrolls browser windows - I use that. You can use the radial touch input on Intuos tablets to scroll/zoom. I just never do. In almost all applications, holding down the spacebar will pan, so again, I use the spacebar.
This is just what works for me. I make absolutely no claim it's "correct" or right for any other user.