I have played with DPI settings a lot. The best fit for me is to set screen size in /etc/X11/xorg.conf.d/50-monitor.conf. That is somewhat tedious as the size is in mm there and the DPI is calculated then. So I had to do the reverse calculation, ie have a target of, say 144 dpi (150%) and calculated screen size from that. My actual dpi is 162 or so but that looks odd. As the gnome folks simply ignore the monitor setting, I also have to set dpi in ~/.Xresources via Xft.dpi:144 along with cursor size. Lastly I set dpi in Firefox for making its UI elements not hurt my eyes.
The pro is that you can set screen size per monitor and thus override any automagically calculated defaults for any of your monitors.