You could put a short reset on it just in case you haven't renewed someone in 10 seconds, it will go back to PoM.
Code:
#showtooltip Prayer of Mending
/castsequence [mod:shift,@party1][mod:ctrl,@party2][@mouseover,help,nodead][help][@player]reset=10 Prayer of Mending,Renew
The way the macro was written originally should work on mouseover with no one targetted though. What button do you have it bound to that it wasn't working?
If you are using a 3rd, 4th, 5th + mouse button, it won't work with unitframes without an addon like Clique\Healbot\Vuhdo to interpret the mouse button to a unitframe.