Via command: /font -z FONTSIZE FONTNAME, ie:
The - in front of the 12 ensures that 12 matches the font size in the font dialog (see /help /font).
Via dialog: Depends where you're setting the font. If you use /font inside a channel window you can set default for channel windows. If you use /font inside queries you can set it there. If you see it grayed out, the window type does not support defaults (perhaps you were trying to set it in a custom window?). Basically, there is currently no global default setting, you have to set it in each window type. Someone
recently suggested a consolidation of these dialogs into one "font central" of sorts, to make it easier to set all of these defaults.