First, if you haven't already done so, find and install the NEOScavenger Save Manager (link available in a number of places, including GOG.com). This gives you the ability to save your game in three different slots, and start over from a saved game after you die (rather than lose your entire game to a bug or an accidental mouse click). This is the single most important thing you can do to reduce your stress.
Second, consider your character build carefully before starting. I find certain skills essential for an enjoyable game, but your mileage may vary. I'm currently using a build with:
Melee (essential skill)
Trapping (essential skill)
Botany (essential skill)
Medic (extremely useful, but not essential)
Eagle Eye (useful, but not essential)
Insomniac (flaw, this lets you get the first four skills for 16 total points)
Metabolism (flaw, take this if you want Eagle Eye as well as the other four, -or- if you want the first four plus Tracking instead of Eagle Eye, in which case you don't need to take Insomniac)
Melee lets you kill the Dogman in the first encounter, make the best spear in the game (Broad Spear) which gives you a reach weapon, and improves your attack/defense/damage in close combat (which is far more common and dangerous than ranged encounters where you can take cover or escape more easily). It also gives you a Leg Trip attack, which might save your life in a desperate fight. To me, this is the most essential skill in the game unless you plan to play a total stealth build.
Trapping lets you skin the dead Dogmen for their pelts, which make the best coats in the game. It also lets you start a fire with just a Medium stick and some Twigs, it lets you craft Squirrel Snares for easy meat and hides, and it helps you avoid traps while Scavenging for supplies. It also lets you cure meat with ashes, so it decays slower (though cured meat will increase thirst as it reduces hunger, unlike plain old cooked meat). Tied with Botany for second most essential skill in the game.
Botany lets you scavenge open fields as well as forests, giving you berries and mushrooms to eat. It also automatically identifies any berries or mushrooms or berries you find, so you don't eat poisonous ones. These are the best foods in the game, in terms of weight/space/nutrition/decay rate. They also do not need to be cooked or sterilized to be eaten, and they reduce hunger as well as thirst. Berries are better than mushrooms, so if space is limited, eat all the good mushrooms you find and carry the berries as rations. This skill also lets you brew Tannin Tea from twigs and water (with a pot or soup can). Tea helps you fight off infections and sickness, and its a valuable trade item. Tied with trapping for second most essential skill in the game.
Medic isn't essential, but its so useful it outshines pretty much everything else. You get a free First Aid kit at the beginning of the game (you find it when you search the Cryo Chamber), which means you start with some clean rags/antibiotics and sometimes even painkillers. The kit itself works as a 4x4 container until you find a backpack or other container. Your healing rate is slightly better, and that stacks with the slightly increased healing rate from the Metabolism flaw (flaw, not skill!) On top of that, you get some extra status bars for your character, showing detailed information about your condition AND it shows you how well any given campsite affects your healing. Finally, you automatically identify any pills you find in the game, which can keep you from poisoning yourself as well as increase the value of any pills you want to sell/trade.
Eagle Eye is useful for scouting from high ground, letting you pick a safer path as you travel, and it gives you a free Multitool at the beginning of the game (you find it when you search the Cryo Chamber). It stacks with a Telescopic sight or Binoculars, to extend the number of hexes you can see during the day. The best defense against a Dogman or any other threat is to see them before they see you, and this skill helps you do that. If you are the predatory survivalist type, it also helps you spot potential victims before you sneak up and ambush them.
As far as flaws go, Insomniac is a very minor one. Just make sure you keep an eye on your hunger/thirst and park in a safe spot before you try to sleep (it will usually take you several tries to get a good night of sleep). Make sure you have a campsite that has a high Sleep bar rating, and use a sleeping bag when you try to sleep. If you find/buy Sleeping Pills ("sedatives" or "Zolpedim", they are blue in color), Insomnia becomes a non-issue. Metabolism is half flaw and half perk - you need to eat/drink more often, but your wounds heal up faster (which stacks nicely with Medic). Having Trapping AND Botany means you will never have trouble finding food and water, so Metabolism isn't much of a problem.
There are some things that you really want to have with you at all times, if you can arrange it:
a Broad Spear in excellent condition (I replace mine when it nears 50% durability). Have this in your hand at all times, anywhere outside Detroit Mega City. Don't start combat without it!
a backpack (whatever you can find - the kid's backpack works well, use a shopping bag if nothing else) Put your first aid kit in here.
a makeshift sack (craft one with string+tarp) this is your main 'loot carrying bag', use a shopping bag if nothing else but there are many things that work as bags
a crowbar with a sling (crowbar+string) slung over your shoulder opposite the backpack. Helps you scavenge buildings, and its a backup melee weapon/meat roasting stick.
cargo pants (cargo shorts are next best) and a hoodie. Both allow you to carry extra gear and wear out really slowly. I put my 'Emergency Gear' in these spots.
Glass Shards. You want the 100% condition ones for your spears, and those come from broken bottles. Never use a 100% glass shard for anything except a Broad Spear.
Telescopic sight on a strap. (take it off a gun, or find it while scavenging. Add a strap made of string, put it around your neck.)
BRONZE TALISMAN NECKLACE - never take this off, never drop/sell/destroy this. If you do, a really nasty monster arrives next turn and kills you.
Berries and/or Mushrooms. These decay really slowly (0.6% per turn), and reduce both hunger and thirst. Berries are better than mushrooms, for thirst.
At least one or two empty plastic bottles to carry water or other small valuable items.
a Soup Can. These are so handy, I made a separate blog post about them.
Boots or shoes that match, and are on the correct foot (Left/Right). Not having these means one less move per turn.
These are the items I carry in my cargo pants, hoodie and my first aid kit. This stuff is the gear that will save your life if your camp gets raided or you lose all your containers to decay or theft. It includes medicine for wounds and illnesses, pill bottles for noise traps, soup can to boil water or tea, shards to make weapons and clothes, string to make slings/bags/clothes/weapons, and a lighter for fires when you can't find medium sticks (use rags or scraps of paper etc).
Cargo Pants (3x3 space)
a Soup Can (holds two pill bottles). You can boil water or tea in this, or make a noise trap from it with some pebbles. I will use the pill bottles as noise traps before wasting the can.
pill bottle (with two stacks of ten pills each,HydrocodoneandAmoxicillin). These two are the most important drugs, they treat pain and infection, so they go in the same bottle.
pill bottle (with two stacks of ten pills each,ZolpedimandLosepine). These two help you sleep and treat vomiting, so they are in the other, less important bottle.
a stack of five Glass Shards (all at 100% quality, from broken bottles). These are to make replacement Broad Spears.
a Flic lighter (the highest quality you can find/buy) A source of fire, as well as a light source when Scavenging.
Olive Hoodie (2x3 space)
The hoodie is usually covered by the Dogman fur coat, so you have to take off the coat to access the hoodie's cargo space.
a stack of 20 Handfuls of String. You can make slings, straps, noise traps, Broad Spears, hide gloves and rag shoes
two Disposable Shopping Bags (the highest quality you can find/buy)
Medical Kit (4x4 space)
This is the First Aid Kit you found at the beginning of the game, carried in your backpack (or your off hand if you don't have a backpack). The stuff inside of it will keep you from getting sick or infected. Even though they are heavier, I prefer to use the glass whiskey bottles, because the glass bottles can be used as a weapon (in extremis), or they can be broken down to get four Glass Shards for weapons/tools. (The different shape reminds me not to waste what's in them, too.)
Whiskey Bottle (filled with 12 drops of whiskey) Never drink this stuff, only use it to disinfect dirty rags and any open wounds you have.
Whiskey Bottle (filled with 2 drops of Sterilized Water). Never sell/drop or drink this stuff. Use it to check any water you find, using the 'stacking trick' to check for clean water.
a stack of ten Clean Rags (for bandaging your wounds).
a Disposable Shopping Bag (the highest quality you can find/buy)
a stack of ten Ketchup Packets. Never sell/drop these, as they are your last ditch food item, and they never decay.