There's not much you need to worry about in S.P.Q.R., but I still recommend defensive play styles while on Legendary.
If you are ever at less then 3/4 health, I would have the Health Boost on. Any other time, the Focus or Damage Boosts depending on how full Focus is. Use it to get yourself out of a jam.
Also, I recall at times when I was at low health, trying to separate one enemy from a larger group would help in order to restore my health. Remember: play defensively.
But most of all, and this goes for any Legendary level, have patience. If you start getting frustrated, walk away for a bit, relax, and then come back and try again.