I'm about 15 hours in, and I think I learned a valuable lesson. I got to Bionis' Leg, and there was a plot event waiting for me to trigger it. I'm not that interested in following a critical path, so I took off and explored the Leg. It took me a few hours but I eventually made my way around the entire area and was ready to trigger the plot. Of course, as soon as I did, it led me to a new area where I got about 25 quests telling me to go do all the things I'd already done. Luckily, I was able to complete all the quests that only involved grabbing items (because I'd picked up everything), but I had to go around and do everything else again.
So: when entering a new area, is it better to trigger the plot and wait until you get a load of quests, then start exploring? That would have been the smart way to do it here. Also, when you get the timed quests (with the clock), is it better to wait until the game tells you that you've reached the point of no return and then double back to make sure you've completed everything? I have a few clock quests now and no idea how to complete them, so I think I need to press on and possibly uncover new areas, but I don't want to go too far and miss them.