Asteroid Impact

Image Credit: Don Davis/NASA
There are millions of objects in space. Most of them are in the Oort Cloud, and despite our best efforts we have been unable to sufficiently catalog them all due to the fact that they are all so far away from the sun, and reflect little light. This makes them practically invisible. Any one of these objects is a candidate, since it is possible that gravitational interactions between the planets may throw some of these objects out of their orbit, pulling them towards the inner solar system. The Tunguska event which occurred in 1908 was a notable recent impact.
A global pandemic
A global pandemic may one day be the cause of doomsday. As more and more of us live in large cities, all packed close together, working close together, we become particularly susceptible to disease. Though it is thought that due to individual differences there will always be about 10 percent of any population who are immune to the diseases.
A geological event

Credit: National Park Service
The eruption of a super volcano would be particularly devastating. The last super volcano event is known as the Toba Eruption and it occurred in Indonesia some time roughly about 69,500 B.C. According to the Toba catastrophe theory, human populations were reduced to a few tens of thousands of individuals by the event. Yellowstone Caldera is just such a super volcano that may go off at any point. If it does the human race is in for a stormy ride.
Energy
Depletion of oil and other natural resources will present a catastrophe for the human race. If we explore other forms of energy then this catastrophe will be diverted, but if we don't then who knows what could happen? It is possible that when we run out of fuel and resources we fall back into the dark ages or the stone ages. While many believe it to be unlikely it cannot be ruled out, and will continue to be good material for science fiction at least.
A gamma ray burst

Credit: NASA/JPL
The majority of observed gamma ray bursts appear to be collimated emissions set off by the collapse of the core of a rapidly rotating, extremely large star into a black hole. A nearby gamma ray burst would be extremely deadly to humanity and could not only strip the atmosphere from the planet, but would also damage DNA so that life was no longer possible. An deadly source is a hypernova, a hypothetical occurrence of a burst produced when a hypergiant star explodes then collapses, and causes vast amounts of radiation to spread across hundreds of light years of space.
Spin
A very abrupt reorientation of Earth's axis of rotation could be deadly for humanity. Fortunately scientists have now established that though polar wander has occurred in the past, it has proceeded at rates of one degree per million years and so poses little threat. Novelists/Hollywood however are very unlikely to be done with this one just yet.
Sunlight
A drastic increase or decrease in the Sun's energy output would be devastating for all life on earth. Unfortunately so little is known about the sun, that it would be very hard to rule it out.
Disappearing
Perhaps the most frightening of all the catastrophes that could happen to mankind would be just to disappear forever. Physicists have been investigating the physical universe and have discovered a number of fascinating things about matter. There are particles for example that just appear out of nowhere and then disappear again. Scientists call these particles virtual particles. What if the whole universe was composed of some kind of virtual particles? One similar idea investigated was that involving a sudden change in the physical constants governing the universe. What we observe to be the physical constants that decide such things as how strong gravity is and the strength of weak and strong nuclear force may all have been created by a vacuum metastability event. Think of our universe as being a ball that can only exist above a certain height. It rolled down hill but was stopped by a bump in the hill and now sits in the dip. Although the universe (the ball) appears in a stable position, in actual fact its position is unstable. Bump it and it will roll down hill further below the altitude at which our universe can exist. Our universe would be destroyed and new laws of physics would appear. We wouldn't even know what had hit us.
Black Holes
As we all know, black holes are stars that have become so big that they have collapsed down under their own weight into a singularity. From this singularity nothing can escape, not even light. If a black hole was to pass by earth it would be game over for us.
War

There's definitely the very strong possibility that we might blow ourselves up at some point in the future. If humanity is to survive at all, then we need to learn to get on with each other. Nuclear weapons, inter-continental missiles, unmanned weaponry and other recent technologies are revolutionizing the way war is conducted. The problem is, these just give us more rope with which to hang ourselves.
Grey Goo
Another hypothetical end-of-the-world scenario involves molecular nanotechnology. In this scenario out-of-control self-replicating robots start replicating continuously consuming all matter on Earth in the process as they build ever more billions of copies of themselves. Ecophagy "eating the environment" was the name given to this process.
Grey goo is a term usually used in a science fiction or popular-press context though it applies to many different variations of the same theme. The worst possible scenario thought up involves nanotechnology getting out into the universe and destroying the galaxy. The goo signifies the large mass of replicating nanomachines, these may or may not appear goo-like. Such a dooms-day scenario may result from a deliberate doomsday device, or from an accidental mutation in these self-replicating machines. Fortunately there are many good arguments as to why Grey Goo may not be such a risk.
Large Hadron Collider
Although a number of people have expressed their worry at the LHC being turned on, the LHC is unlikely to present a doomsday risk due to the fact that collisions with the same energy as the LHC occur in our upper atmosphere all the time and since the earth continues to exist, there appears to be little danger from these energies. For more about the LHC go here: Big Bang Experiment
Aliens

The final scenario is one that has been played out often enough in Hollywood and Science Fiction movies. With this in mind, rather than write a screed on the subject, we end with a fascinating depiction of it! Can you guess where the image is from?