Another down-side to using embedded fonts for small-caps -- if you use the small-caps font for only small portions of text, it won't necessarily look well with the user's chosen font.
If you use embedded fonts for the entire body of text, the user is likely to call down maledictions on your head for pre-empting their choice.
I do happen to frequently use semi-serif fonts (like Fontin or Marcellus) that "sort of" blend in with either serif or san-serif body text, but it is not the happiest solution. So I try to use them only for fairly isolated small text fragments, like letter salutations and signatures, signs, etc.
PS -- I almost forgot another reason for not using multiple spans -- in some ADE-based readers (and others?), moving in and out of spans sometimes causes broken lines. Lots of discussion on this thread:
https://www.mobileread.com/forums/sho...d.php?t=232395
Especially see Hitch's post # 26.