The main issue I have with Windows 8 is that when you attempt to move the mouse cursor from the left monitor to the right, if you're too close to the corners on the left screen then you get the charms bar appearing. You can disable the charms bar on the right monitor, but I think I'd prefer to disable it on the left one. I'm sure this can be tweaked, though.
There is one other issue - if you wish to open a piece of software via the "Metro" interface twice, you need to open the second copy as a new window. I don't think this is an issue if you religiously stick to desktop mode.