You should probe everything, from a planet/moon. Probing from a Heph tells your target that it might be on the way.
When you find a good cluster of targets, you've found a destination.
Alternatively, pick a galaxy and start at the bottom or top, and slowly work your way through to the other side. If the galaxy is packed, move 20-50 systems at a time. If empty, stop only where there are vacation spots.
Keep Gaia's on board, and do any harvesting from a MAC. Harvesting from a Heph can be dangerous. If you must harvest from a Heph, use Zags instead of Dios.
Keep lots of fuel on board.
If attacking a planet outside the system your Heph is in, unless there's noone around who can pose a threat, try and avoid sending anything as slow as a Prometheus. The faster the better.