The body snatchers. In the 70s version, they have overwhelmed and supplanted the human race before we even knew they were there.
Well, yes, but was it an “alien”? More like a badass computer virus. 
What is this referencing? It sounds awesome…
Haruhi Suzumiya. It’s very funny really. Nobody – not even Suzumiya herself – knows that reeality was destroyed 3 years ago apart from the three agents sent to watch her, and the narrator Kyon who has been told what’s going on by the three agents. The danger is that Suzumiya will get bored, and destroy reality again, so she has to be kept from being bored. But she really has no idea about her powers, or about the people watching over her: she thinks they are just fellow students that she recruited to her high-school club.
The Posleen in John Ringo’s “Aldenata” books wiped out 99% of humanity. As an added bonus, they ate a lot of us.
I think you’re referring to “Forge of God” and “Anvil of Stars”.
How many planetary systems have the Borg assimilated?
I gave up on Voyager after about 3 episodes, so I don’t know what their final outcome was.
Actually, in the original book, they weren’t all that badass at all. Yeah, they outmatched us, but we could still dish it out to them, too. There’s at least one tripod destroyed by a direct hit from an artillery piece, and a single Royal Navy ship (the Thunderchild, which has to be up there as one of the coolest ship names ever) managed to take down two by itself.
Later honored by Star Trek: USS Thunderchild | Memory Alpha | Fandom
The Borg in Star Trek: First Contact, in which the Thunderchild appeared, had conquered and assimilated Earth in an alternate future. That’s pretty hard-hittin’. I’d almost rather be dead than enslaved by the Borg.
In John Varley’s Eight Worlds universe (Steel Beach, et al), aliens from Jupiter wiped out Earth leaving only the scattered Moon and minor other colonies for humanity. They were pretty much omnipotent, and humanity never even considered retaliating, just decided to huddle quietly like mice hoping never to be noticed again.
Certainly not #1 after reading other suggestions here, but what about the one single Douwd who destroyed all Husnock in the TNG episode “The Survivors”?
Actually, reading the OP, I immediately thought of the “hard hitting” aliens from Niven’s “Footfall”. Sure, others can blow up the planet, but they threw a giant rock that hit the Indian Ocean and wiped out something like 25% of humans. (And they had lots more rocks if they needed them.)
My recollection of those books is that
[spoiler]Earth was evacuated and moved, but it is still around. A couple of characters get mysteriously transported there (for a scene paralleling the death of Keats, I think). Also, doesn’t whats-her-name do some of her teaching to a group of people there in the “future”, before she has to loop back into the rest of her life?
And those were computers that threatened Earth, anyway, not aliens. Although maybe they’d evolved to the point where they counted as aliens.[/spoiler]
I thought of “Footfall” too.
But for most casualties I submit the Iridan-Culture war in Iain M. Banks’ Consider Phlebas. There were a total of ~850 billion casualties on both sides, and though the Iridans were the ultimate losers they must have been responsible for a fair proportion of the total.
Varley had an even more overwhelming alien invasion in his short story “Just Another Perfect Day”. The aliens in that story existed outside of time. When they invaded Earth, they invaded throughout history simultaneously.
[spoiler] My recollection is that you don’t know the Earth might not be destroyed until the end of the series. For most of it, the Earth is Toast.
For that matter, by the end of the Hitchhiker’s series, the Earth is back. Seems like nobody REALLY wants the Earth destroyed.
Wimps.[/spoiler]
In Joe Haldeman’s terrific short story “For White Hill,” aliens who hate us
[spoiler]release fast-reproducing nanobots which target and consume all human flesh, then mutate to kill all living tissue everywhere on Earth. Humanity isn’t wiped out, as there are two dozen or so colonies elsewhere in the galaxy by then, but everyone here dies and the planet is rendered completely sterile, a catastrophe like no other in human history.
The story focuses on two artists who take part in a juried competition on Earth decades later to commemorate the tragic event. A sad, wonderful, lyrical story - highly recommended.[/spoiler]
There’s the Rikti from the game City of Heroes, who on several timelines destroy all of humanity on Earth. Amusingly, I understand that’s canon for what happened to the world the beta version of the game was set in; they invaded again and killed everyone.
The Achuultani of the Empire from the Ashes trilogy destroyed two human interstellar empires, with only a single planet surviving both times.
In the Bolo universe, the human-Melconian Final War killed off most of both species, in a war that devastated much of the galaxy.
In *White Dwarf *I read a battle report where the Imperial Guard faced the Hive, I remember the Guard winning and his closing statements were, “we sustained an acceptable casualty loss of 96%” THAT’S badass.
A couple of characters in Larry Niven’s The Ringworld Engineers have to sacrifice 5% of the population to save the other 95%.
IIRC that 5% amounted to more than one trillion inhabitants.
Love the way the OP adds the ‘in fiction’ part. To avoid confusion?