If you wish to keep your sanity through the entire game, I suggest only doing the really big side quests and ignoring the majority of the others. The game is fucking huge, and it can easily become repetitive doing everything.
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I would say do every actual sidequest but don't bother clearing the map of all question marks. Hunting for Witcher school gear is also just mostly cosmetic and optional, but they're the coolest armors and swords.
Also, if you're not playing on the lowest difficulty, read the infos in your journal regarding the creatures and prepare accordingly.
I try to get everyone to try playing on Death March, no fast travel.
I did my first playthrough like this. There's so much to see in the world and so many paths to take. Fast travel is neat and all but you may miss out on so much. I took it a step further and also didn't leave regions/nations until I completed the map. I found more incidental quests by taking a wrong turn or a shortcut over a hill than I did by following the main quests.
On Death March: It's actually not hard at all and feels like how the gake should be played. What it actually does is forces you to look at the bestiary, learn or guess weaknesses and attack patterns then use potions, spells and pils to fight enemies. It actually feels like playing the witcher as lore accurately as possible. Going to the local herbalist, buying supplies, meditating then hunting down the enemies.
I disagree, it made the enemies become tedious damage sponges and currently making the game less enjoyable.
This isn't a Souls game. Whatever difficulty setting is one/two below the hardest is an acceptable balance between completely wasting my time or challenging fun.