Fallout 2 has a healing device called a Super Stimpack, which heals massive damage instantly, but has a timer that inflicts some less-serious damage later on from harsh drug side-effects. It is possible to assassinate the Enclave's president by healing him with about ten of them. There is a special text message for this eventuality.
Along the same line, you can use the drug Jet on the enemies to cripple them before a fight. Jet is a very powerful combat enhancer, but after about 10 minutes of game time, gives you very big penalties. You can use 3 Jet in the Enclave base on every soldier, wait about 30 minutes, and every soldier will be effectively blind and cannot hit you at point blank range.
One of your allies, John Cassidy, has a heart condition. Jet works by accelerating the body's systems. Making that ally take Jet will give him a heart attack and kill him.
The last level in Fallout 2 is supposed to be a running shootout through the Big Bad's home base. However, if you have the same kind of Powered Armor the Bads use, you can drop off your allies at the San Francisco docks and bluff your way through the entire mission, save the battle at the end. Which you can allow temporary allies and base guns to deal with instead of handling it yourself. Sadly this trick doesn't work with random encounters during the rest of the game.
In Fallout 3, using the pickpocket command to deposit a grenade or a mine in another person's inventory will a) automatically activate it and b) give you an achievement for doing so.
Early on in Fallout 3, you are given the opportunity to do a fairly long sidequest that is essentially an optional, extended tutorial, one stage of which involves investigating an old robotics factory. Another sidequest, normally started much later, involves two "superheroes," the AntAgonizer and the Mechanist. There is special dialogue for accepting the sub-quest to go to the robotics factory while wearing the Mechanist's costume.
Remembering that the AntAgonizer is based on a comic book character, it's possible to use info found in the publisher's ruins to make her give up her life of villainy.
If you talk to Stockholm (a sniper in Megaton who is normally unreachable) by using the command console to make yourself fly (or give yourself godmode and launch yourself upward with a mini-nuke and land just right), he will chat like other NPC's, and end the conversation with "And how the hell did you get up here, anyway?"
There are actually two Stockholms: one for the Megaton city cell itself, and one for the overworld outside Megaton. They are actually two separate entities (albeit with identical appearance and dialogue). Killing one will automatically make the other disappear.
One of the DLC packs for the game requires you to talk to a few Brotherhood of Steel renegades called the Outcasts. After helping them with a Super Mutant problem, you almost immediately engage in conversation with them. If you happen to be wearing armor that you took from the dead body of an Outcast elsewhere in the game while they talk to you, they start asking what the hell you're doing off-duty.
Speaking of the Outcasts, there is an unmarked sidequest at their base of operations where the Lone Wanderer can trade certain items for meds, ammo or grenades, if the player has failed to earn their leaders trust by turning in enough technology; Their leader will confiscate any Outcast Power Armor the player is carrying, stating it was rather convenient that you "found" their armor out in the wastes
If you kill Lucas Simms, the town Megaton's sheriff, his son will have new dialog options with you. Moreover, if you start wearing the Sheriff's outfit, his son will say "You might wear this badge, but you're not my dad." Other NPCs will react too!
Lucas Simms will more than likely die, if you side against Mr. Burke in the quest The Power of Atom, during a cutscene of sorts. "Of sorts" indeed, because nothing keeps you from acting during it, and disarm or execute Mr. Burke before he gets the chance to fire his one-hit-kill scripted bullet at Simms. The sheriff himself even thanks you for saving his life, praising your quick reflexes. And your VATS, probably.
The Power of Atom, in which you either disarm or detonate the nuke in Megaton, is likely one of the first quests you'll get in the Wasteland, and is usually done right away as it results in the only available player housing in the game. Holy Water is a quest that is only available near the end of the game after the main quest is complete and you've begun Broken Steel content, and it starts just outside of Megaton. If you somehow happen to blow up Megaton while Holy Water is active, there is a set reaction from every NPC involved.
Similarly, if you've already started the Wasteland Survival Guide quest for Megaton resident Moira when you decide to blow it up, upon returning to its ruins you will discover that she was out of town when the bomb went off. The radiation has turned her into a ghoul, but you can still finish the quest for her. However, after a few in-game days, Moira will relocate to Underworld, since ghouls fit in better there... which can get her killed.
If you blow up Megaton and then save your father, he'll confront you about it. If you lie and claim no involvement, he'll express relief - after all, he can't bring himself to believe his child would do such a thing. If you admit it or try to justify it, he won't buy your arguments.
If you find James independently of the Galaxy News Radio subquest, either by Sequence Breaking or passing Three Dog's speech challenge, you still have the option to go back and complete said quest, which rewards you with a key to an otherwise inaccessable weapons cache in Hamilton's Hideaway.
Uncle Roe will tell you that he "hasn't heard from (caravan merchant's name) in a while" if that merchant has died, and you will no longer be able to invest in them. Although if their pack brahmin survives, it will continue to follow the caravan route, and you can loot the inventory if you retrieved the dead merchant's key.
Fallout New Vegas
The opening cutscene depicts you being shot in the head, and left for dead in a shallow grave. Later on in the game, you can actually obtain the weapon used to do the deed, Maria. The aforementioned weapon doesn't do quite enough damage to kill the Courier in a single critical headshot at full health, even if the Courier is level 1, unarmoured, and has SPECIAL stats of 1 and skills of 0 across the board. Furthermore, upon obtaining the weapon, it will always have full durability minus one shot's worth, this being the shot placed in the Courier's skull.
In Fallout: New Vegas, in a mission given to you by The King, you have to investigate a bodyguard named Orris, that seems to be doing his job a little too well, he does this through paying thugs to play dead while he fires blanks, giving the illusion of skill, but if you decide to go back and attack the thugs on the ground, they get up and yell, "Orris 'aint payin' us enough for this!", and attempt to kill you.
If your character is too dumb to figure out the scam (low intelligence, low medical skill) then The King will be pissed off and make you do it again. Only the next time, Orris won't fall for it and will try to kill you off the bat.
Faction leaders Mr. House and Caesar tend to congratulate (or scold if the player did something to annoy or anger them) the player on things they have done. Mr. House, for instance, will praise the player if he immediately goes and retrieves the Platinum Chip instead of talking to him, while Caesar will offer praise if the player kills Mr. House as soon as he enters the Lucky 38.
Caesar in particular will give an absolutely epic rant if you've been working against his interests earlier, listing each and every blow you've dealt to his forces and finishing with asking you why you felt it safe to show up in his tent.
You can then respond that you came to "decorate the inside of this tent with your guts", causing his bodyguards to cower in fear before you blow his head off.
Almost all of Mr. House's dialogue has a corresponding line from Yes Man. If you kill House and install Yes Man into the mainframe before going after the Platinum Chip, it will be Yes Man that greets you inside the Securitron Vault. He will also give the demonstration on what the Mark II upgrade does in House's stead.
Alternatively, if you pursue the independent ending without upgrading the Securitron army, he will scold the player (as best he can anyway, given his programming) for trying to take on Caesar's Legion and the NCR without a standing army.
Whenever you have a companion, try to give them an order you already gave them a few seconds ago and see the results.
Raul: Right. Got it. I'll just stop using this melee weapon and instead use a melee weapon. Good idea, Boss.
Dropping the (hard-to-find) radiation barrels on Cottonwood Cove will result in the Legion ferryman donning a radiation suit on subsequent visits.
Bypass Nipton on the way to New Vegas, thereby avoiding meeting Vulpes Inculta. Once you get to Vegas and meet Vulpes Inculta, kill him, then go all the way back to Nipton. A uniqu Legionaire named Gabban will be in command at Nipton instead of Vulpes that you can talk to instead.
Likewise, if you kill Vulpes in Nipton, he will be replaced by Alerio on the Strip and at the Fort.
In Dead Money, you can find 12 skill books, one for each skill except Survival. Survival's book? Fallout 3's The Wasteland Survival Guide, which hadn't been written when the Sierra Madre was constructed.
In Old World Blues, a required quest involves you entering a chamber containing Gabe, the cybernetic dog of Doctor Borous while he was still human. Gabe is hostile and immediately attacks you. You'll almost certainly be forced to kill him, but you're not required to, and even if you dig up the item you need from one of a dozen dirt piles around the chamber, roboscorpions will attack and almost certainly kill Gabe if you didn't. But if you did avoid killing Gabe and protected him from the roboscorpions (neither of which the game even really hints is possible), Doctor Borous has unique lines thanking you for sparing his dog when you bring Gabe's bowl back to him.
There is a quest where you can kill three Fiend leaders and bring their heads back to Camp McCarran for a bounty. Major Dhatri who gives you the mission will explicitly state that he can't give you the full bounty reward if the heads you bring back are damaged since they can't be entirely sure that it's actually the person the bounty is for. If you do any damage to Cook-Cook, Violet, or Driver Nephi's heads before killing them, you end up with their mangled head (which nets a lower bounty reward), but doing no damage to their heads give you their normal heads. Exiting the inventory box after taking the leader's head off of their dead body will be followed by a rather disgusting squelch and cause their head to disappear from the ragdoll (the squelch sound happens even if the Fiend was decapitated in the fight though).
One of the NCR quests involves resolving a conflict between the NCR and the Kings, and one way to resolve it is to kill a King named Pacer. You need to make his death look unconnected to the NCR, so you need to either arrange for him to die by accident or get him to be (or appear to be) killed by the Van Graffs. There's a pretty impressive range of options, such as simply killing him with an energy weapon, spiking his Jet with Psycho to cause him to have a fatal reaction, slipping an energy explosive into his pockets, or even forging a hostile note from the Van Graffs and sticking it on his Jet stash, which will cause him to run off and attack the Van Graffs. The kicker here are two options that aren't readily apparent: if you killed the Van Graffs already, you can tail Pacer to their building and kill him with an energy weapon inside the store. Alternately, you can take another sidequest where your job is to stand guard outside the Van Graff's store in Van Graff armor and using an energy weapon, and then deliberately picking a fight with Pacer when he walks up to the door. There is nothing in the game that hints that this latter option is possible, but it works perfectly fine for the quest.