I use workspaces AND multiple monitors. No, not in Xinerame.
e.g. when making a webpage, I can work on one monitor and see the result in another.
I can then still switch on one monitor to some other set of tools and not change the second screen. So why not both?
This is also the main reason I use XFCE and not KDE/GNOME because if it is possible to configure it, it is darn hard to do and much easier to just use XFCE where it works out of the box. Last time I checked, KDE and GNOME use something similar to Xinerama, which means that when I switch on one monitor, the other changes as well.
Small downside of how I do it. I can't move a program from one site to another and I need to have two profiles for Firefox, because you can not otherwise lauch Firefox on each screen.
So I say: do both and leave the choice to the user. I have three monitors and 6 desktop on each.