A/N Written for a prompt that asked for the various ways in which Sherlock would go about killing his friends. I probably had way too much fun with this idea. Hope you enjoy :)
Disclaimer: I do not own Sherlock, which is probably for the best.
Lestrade
Sherlock isn't lying when he says the Detective Inspector would be easy to kill. The man has no qualms about Sherlock knowing his address, insists on a regular (boring, human) sleeping pattern which leaves him incredibly vulnerable and his line of work practically demands a target be placed on his head. How Lestrade reached the ripe old age of fifty, Sherlock will never know, but he certainly didn't manage it by skill and a deep sense of self-preservation. So when Sherlock is especially bored and plans the murder of his friends to pass the time, he finds himself with an infinite amount of options in which to dispose of the DI. So much so that it's almost tiring trying to rank them all.
Sherlock does rather like the man, so something relatively painless would be preferable. And then there's the possibility of evidence, and Sherlock wouldn't particularly want any leading back to himself (Donovan's face would be a picture though) so something as intimate as strangulation is crossed off the list. There's Lestrade's job and the dangers he's faced before – Sherlock has been at his hospital bedside for injuries ranging from broken bones to gunshot wounds – so it'd be easy enough to paint the death as simply an unfortunate run-in with a criminal should that excuse be necessary.
Eventually he decides on a gunshot to the back of the head from a distance. It's painless enough to leave some of Sherlock's conscience intact and has the convenient possibility of being narrowed down to simply a common criminal out to get a rather influential Detective Inspector. Done.
It's at this point that Sherlock usually stops thinking about it because, as entertaining as lining up all the variables may be, he is rather fond of Lestrade.
And the lack of new cases following his demise would likely drive Sherlock to insanity, so it's probably in both their best interests that the man keeps breathing.
Mrs Hudson
Initially, Sherlock wondered if shocking his landlady into a heart attack would be possible should her motherly ways ever extend beyond mildly infuriating. However, the woman had proven over time that she has a rather impressive threshold for extremities; growing accustomed to finding all manner of body parts in the fridge and her past experiences with hostage situations would make shocking her a rather difficult - and tedious - task.
Instead, he decides that poisoning her would be considerably easier. With her constantly making tea that may or may not be drunk, baking cakes in her many hours of free time and preparing meals three times a day (far too often, in Sherlock's opinion), slipping some ricin or a small quantity of clostridium botulinim into her food would be a simple enough task. If he managed to distract her with talk of his latest case or her rather eventful marriage, she'd be so distracted she wouldn't even notice him doing it.
Simple enough, really. He decides against it, however, as he does rather like his morning tea.
Billy
Billy would be so easy to dispose of that thinking about it barely takes three seconds. An increased concentration of his preferred cocaine solution and he'd overdose without even realising anything was wrong. Boring.
Mary
Mary may be an interesting challenge, if murdering her ever became a possibility. Her past dictates that killing her would not be so simple as a bullet or spiked drink, and she'd be perceptive enough to notice that Sherlock was planning something dastardly.
He could exploit her weakness for John, he supposes. Stick him in a hostage situation, demand she come alone to save him only to send her running towards her death. No, that would never work. Perceptive. She knows Sherlock too well - John is a weakness shared between the two of them after all - and he's as likely to threaten the doctor's life as he is to fall in love with humanity. So that idea's scrapped fairly quickly.
Even more maliciously, he could exploit her past. Magnussen claimed to have contacts, and while they may have existed only in his mind, it is likely that they can be found if one digs deeply enough. Sherlock wouldn't even have to pull the trigger. All he'd need to do would be to make a phone-call and wait for the inevitable fallout.
But then, he would never do that. Sherlock doesn't particularly trust the woman, but he trusts her devotion to John. Killing her would ultimately harm his best friend and even in an imagined scenario, he is unwilling to allow that.
Besides, she's a good ally to have. He just has to ensure that they stay allies in order for them both to stay safe.
Mycroft
There are a great many hypothetical ways in which Sherlock could dispose of his brother should the temptation ever reach breaking point. And hypothetical they will most likely stay, for Mycroft is nothing if not infuriatingly brilliant and trying to trick him with a poisoned cake or an ambush is as likely to work as simply spraying him with a water gun. It is probably of benefit to them both that Sherlock's attitude towards Mycroft has never quite delved into murderous intent– he can only imagine what Mummy would think.
There are times, however, when Sherlock can't help but wonder what will finally cause his brother to fall. In his line of work, old age is a blessed rarity and his overly protective manner towards his little brother is an occupational hazard if ever there was one.
It's in the rare moments where Mycroft's cold mask slips into something approaching concern, that Sherlock realises he can spot his only true weakness - the true key to his downfall. The disappointment in his eyes after Sherlock's first overdose, the regular calls during his two years of gallivanting to ensure that Sherlock's head hadn't had an unfortunate date with a bullet, the utter panic in his voice when he'd practically begged his men not to fire at his little brother on Appledore's steps.
It all leads to a natural conclusion. Much as he loathes to admit it, Sherlock finds that the most effective way to kill Mycroft would probably be to kill himself first.