The most universally accessible fonts will always be "monospace," "serif" and "sans-serif" and the styling you do would incorporate size, weight, style and variant. Line height will manage the spacing between lines.
There is no magic rule for choosing fonts and styling. Pick what looks good to you (and hopefully to other people) and make sure that you back up any non-standard fonts with a universal font.
This is a pretty good reference for choosing cross-platform fonts.