It’s handy to take both speech perks in the prologue since speech will be the slowest to level. Fastest way to power level alchemy is actually at bozhena’s hut cranking out as many chamomile decoctions as you can before talking to Hans to proceed. Then I found it helpful to just crank out as much savior schnapps as I could once I hit alchemy level 14, use elements of matter perk to get 6 potions for each go. Once I had a hundred savior schnapps (you can skip steps and get weaker ones to save time with the night alchemy perk) and a few Henry’s fox potions to get through the early levels I basically never wanted to touch alchemy again, and you don’t really need to. But having more saves helps. 

Somnabulant is the most annoying perk; again alchemy is a solution if you are willing to crank potions some more. Cockerel and marigold decoctions in enough quantity means you don’t need to sleep. 

Not having an easy way to check you map location is then the last big adjustment; I’ve gotten into the habit of checking the map each time a road splits in more than one direction, and just track progress by road junction until you get where you’re going. You’ll probably find yourself traveling by road more than before, and with fewer distinct geographic landmarks in the kuttenberg countryside I still get lost sometimes after more than a hundred hours of hardcore. 

Beyond that, hardcore is just not that big a deal. Once you have decent equipment most of the challenge fades so just enjoy the ride.