Caves of Qud

Important Information

Before you do anything else, go into the Help section and read the following entries:
- Ten Things You Should Do When You Start To Play
- Skills and Powers
- Weapons and Armor
It's recommended to ignore the other entries, their subjects are mostly fairly self-evident. Combat is a good help entry to read after playing the game for a while, but won't be very easy to understand before playing the game.
There's an official discord. It's a good place to get help or advice.

Try to get at least 18 strength/agility/toughness on basically every character you make.
Mutants have the easier early game, if you take the right mutations.
Not all mutations benefit as much from investing in them. Some reward high investment, some are more or less buy-and-forget.
If you take a bunch of mental mutations and jack up your ego stat to make them all ridiculously supercharged, extradimensional psychic assassins will come to take your soul. They get pretty scary.
True Kin can eventually get multiple wizardnetic enhancements but they have a generally rougher early game, so keep that in mind.
Don't try randomized character builds as a beginner. You will suffer.

The most recommended first quests available in Joppa are those Argyve the inventor gives you. You can and probably should complete all the Joppa quests before moving on, though.
You can steal from some of the chests in Joppa, if you make sure nobody can see what you're doing.
There's something weird about the northwest pool in Joppa. Take a closer look.
Visit the sultan shrine.

Swift Reflexes, Spry, and Hurdle are defensive skills that every character benefits from.
Wayfaring is also more or less in this category, as it helps you to avoid getting lost right into a lethal ambush.
Warning: there are many skills that are in need of tuning or that are outright broken.

If you do something to piss off people you have good rep with e.g. you took something that belonged to them and now they're all hitting you, just... run away. Be somewhere else for a few days. They'll return to being friendly in a while.
"You see a croc and stop moving." Unfortunately the croc is green and so is its background and so technically speaking you cannot in fact see the croc. How do you find it? Hold down the alt key. This also works for finding containers (except baskets for some reason), items, and sultan shrines. And it keeps track of immobile creature locations. Very useful.
Daggers and trade goods tend to be the most encumbrance-efficient way to carry water around early on, armour the least. Make inventory management choices accordingly.
The water ritual can let you buy skills, items, secrets, and even allies with your faction rep. Don't sleep on it.
On that note, don't sleep on sources of secrets in general either, theyre very useful.
If you get a disease, the mayor of Kyakuya has a book for sale that contains recipes for cures.
Sources of limb regeneration are not exactly easy to find in Qud. Try to lose as few limbs as possible if you don't take the overpriced regeneration mutation or are True Kin. Theres a main quest location with guaranteed regeneration access but it's pretty dangerous.

(good as of 10 March 2018)
BEQMMMEMBLBOBPB1DN aka "The Minotaurtaur". Take skills to get the ability to charge and hit an enemy with your axe, shield, and powerful horns all at once and basically just ruin their entire day in one action.
BJQMMMEMBCB6BIBUCBDKDN aka "Scum Turtle". This guy is basically cheating. After a couple levels, you can freeze dudes solid and fart out sleeping gas if in a sticky situation your shell can't protect you from.
AITMMKKK13 aka "Hokuto no Qud". Punch dudes' lights out with your uncapped penetration bonus wizardfists. Punch them through walls. Pump strength to punch them even harder. Take strength drugs to punch them hardest.

You can turn off permadeath in the debug options if you have trouble getting out of the early game and want to see the rest of the world.
You can set debug commands to keys in the Key Mapping menu for cheating yourself out of holes and growing back limbs and such.