I leave mine all the way up, with mouse speed turned all the way down, all the time. You can tell what setting it's on by looking at the little LED inside. Off is the slowest, so you can use that to calibrate it.
I also have 3 monitors on that computer: 1920x1200, 1600x1200, 1920x1080(TV), and have no problem zipping across them with those settings.