The fatigue point from unarmed combat damage only applies if you inflict at least one point of damage AFTER armour and toughness. Yes, it is much harder to KO someone in power armour with a bare fist! It is likewise harder to inflict a brutally painful blow on a 150kg pile of muscle and bone mass than it is to do the same to a 50kg Schola-runt. This means that your 5 year old sister is statistically much less likely to slap a UFC cagefighter silly than a grizzled Imperial Guard Sergeant standing in for your sister would be. This is a GOOD thing!
Takedown is esentially a modified use of the Standard Attack action. You resolve the attack as normal and then if you manage to score at least one point of damage after soak, then the damage is ignored and the target makes a Toughness test instead to try avoiding a nasty stun.
Critters with Natural Weapons do not inflict the bonus fatigue point, as they are not fighting unarmed. The point behind unarmed attacks bringing some fatigue damage with them was to allow for some non-lethal barroom brawls to break out in your game. Otherwise you would have to put someone into criticals before the fatigue starts to show up, and torn off limbs rather obviously trump a black eye and bruised knuckles on the medicae triage list.
Because of scheduling issues my group tends to meet about twice a month whenever we can work out a common day/night, and we run LONG! By long I mean start before sundown and stop well after sunrise often.
Everyone has their own little quirks and moments that bring them gamer-bliss, so I try to include little bits and pieces of things I think they will appreciate, enjoy and otherwise make the game memorable and special for them. Characters personalities and motivations are heavily tapped to make things something more than just some random mission. This stuff is PERSONAL!
I mix in a healthy dose of mystery, intrigue, epic scale backdrops with micro-scale stories in the foreground, hands on investigation, moments for special skills, training and unusual backgrounds to shine. My villains tend to be deeply offensive to at least one of the party's sensibilities. Not necessarily my PLAYERS' sensibilities, but at least one of the characters should be OUTRAGED and trembling to deal out the Emperor's Justice on the offending baddie. Mix things up. If the last three "big bads" have been awful killing machines with demon weapons and vulnerable only to a holy melta-gun during the full moon, then perhaps the next villain should be some insane scribe who wishes to offer up knowledge to the Emperor by burning every book in a vast library that (just happens) to be the secret library of an Inquisitor! Holy fire purifies all, purifies the humble text for He who dwells high upon Terra that he might learn every letter! My acolytes serve an Ordo Hereticus Inquisitor, but sometimes investigations into some reported heretical cult are in fact a stealthy xenos plot to do "bad xenos stuff". Worse, perhaps the fairly harmless looking simpletons are actually in need of a good Maleus investigation? The idea is to keep them guessing, while not suspending disbelief. Your plot twists should make sense, maybe not at first, but once they uncover enough clues the little murmurs of "holy crap, are they connected to those weird heretic monks from 3 cases ago?" will bring little happy GM moments. That look of dawning awareness as one or more of them figure out what they have stepped in this time around.
Personolize it. Make it mean something for the characters. Obviously the evil plots and schemes do not all revolve around them. Far from it! They are holy instruments of the Emperor's divine wrath, though troubled and human. Total abject bad-buttock skull crackers on a mission and serving humanity in secret, at great personal expense. They are but tiny cogs in an impossibly vast organization that spans the galaxy, but the workings of the smallest cog is vital to the smooth running of some giant metaphysical clock. They are meaningless dust, yet they are vital!
I like to mix in some comedy and light elements to offset the terrible gothic horror in sometimes absurd ways, often with memorable NPCs, bizarre scenes or just amusing contrasts. Vividly describing both tragic and glorious moments for individual characters also really helps set the mood. Also, steal shamelessly from anime. Trust me, this works great as long as you are careful to select suitable shows. Dry, dark humour really sets the mood for DH, so be shameless about it if it improves the entertainment value of the game in thematically appropriate ways. Yes, stupid, criminally ignorant gits in tattered rags spouting off junk science to the Adept and Techpriest to show how educated they are in the miraculous ways of maple syrup is just **** funny! "It's a miracle substance, it is! Cures bunions and warts! Makes paper stick together! Let's see ordinary spittle tackle that job, mate! Not up to tha' task, that's whatfore..." It is even funnier if the ignorant bastard actually has a useful skill burried in all that rubbish.
Our Techpriest is played by someone who was a 40K virgin when characer creation started and is now totally immersed in the Cult Mechanicus. His laptop now proudly displays the Omnisian Skull-Cog emblem and you would mistake him for a long-time Mechanicus otaku. The big meat-mountain guardsman on the team is wrestling with exactly which types of heretics and xenos he hates MORE! Oh, he hates them all, and it started with orks, but his list is growing! The far from athletic Schola-trained adept cheerfully wades into combat alongside the heavy hitters, smiting His foes in humble yet effective ways and is developing into an interesting person. Our noble cleric is a bit of a party-girl and was sent to the Tarsan chantries to shape up... Instead she ended up working with the Inquisition using her natural charisma and ability to drink like a Kennedy to uncover secrets. The Scintillan assassin is a Hong Kong action cinema anti-hero, doing horrible things to bad people with many, many empty brass shell casings trailing in his wake as he dreams about the interesting women on his team that are all above his social status. Then we have the noble Cadian guardsman who is their Inquisitor's designated Primus, professionally and stylishly dispatching the Emperor's many foes with lasgun and sword, giving focus to the team and shouldering the sometimes unpleasant burdens of Inquisitorial decrees so her team can focus more on what they love: Doing awful things to awful things!