From the perspective of usability, Hissp is very minimalistic overall. Whereas Hy is both much more Python-like in its user experience and provides much more of a batteries-included experience like you'd find in Common Lisp or Clojure (and in fact its standard library takes a lot of inspiration from both).
I consider Hissp as more of an interesting experiment in language design than a practical programming language. Whereas I think Hy is very practical and I've been very happy to use it for various scripts over the years.
That's not to say Hissp is a bad project by any means. It's impressive, and I admire its dedication to its own principled consistency. I just don't find it very practical.
The downside of Hy is that they've gone through several radical design changes over the years, but that finally seems to be stabilizing.