I think there's a programming issue with the Orion Guardian. I've run into the same issue in more than one game. In my last game I sent a fleet of titans equipped with ~150 missile launchers each (the last ones you research, I think they're called Pulson - the description says they bypass shields) and the Guardian shrugs them off 90% of the time. In that game I chose tactical combat (the combat odds indicator was 90% or more green in my favor) and the Guardian proceeded to destroy all my titans and took 0 damage. It looked as though the missiles were disappearing about half the length of the guardian away before impact. So I reloaded and chose the option to auto-calculate the results and was able to destroy it and lost one of my titans.
In my game today the same thing happened, and this time I had sent more titans than I had in the previous game. Again I reloaded and chose to auto-calculate the results, but this time the outcome was the same - I lost my entire fleet. I ended up withdrawing my fleet and equipping them all with beam weapons at a cost of 150-200k credits, and this time they destroyed the Guardian effortlessly and took no losses. If the Guardian is supposed to be immune to missiles so be it, but this acts like a bug so I'm reporting it.