Cleartype should always be enabled (especially if you have an LCD monitor), so once you do that all fonts should look nice. However, research does prove that serif fonts (like Times or Georgia) are easier to read because of the curves they have and sans serif font put a little bit more strain on your eyes, because their characters don't 'flow'.(well I've read about this... so I don't have a link or anything like that except the wikipedia one).

However according to me, if you plan on reading the text on the computer then i think sans-serif fonts look the best, and if you are planning to print something out (like say, print out the e-mail) then serif fonts are better (that's why newspapers, books etc use serif). And like William says it should be about 12px, so that you don't need to strain a lot.