couple of things, serene 1.3 version just downloaded from w.org:
1. in content.php line 20 and 32 you use this conditional
! is_single() || ! 'video' !== get_post_format()
not sure maybe I'm in a dumb moment but what about this:
! 'video' !== get_post_format()
wouldn't be better just:
! is_single() || 'video' == get_post_format()
2. the serene_post_meta_info() prints out a link which is nested inside a parent link "et-main-image-link"
so you have 2 nested links, this makes the whole area of the play icon (et-play-video) totally unclickable for me, tested in Chrome and Firefox.
Strange enough, this doesn't happen on your demo on elegantthemes.com
Greetings from Italy and congratulations for your review on wpmu :-)