An event that would seriously render a large population as dead, as in lets say only 10% or so are alive.
There are very few potential disasters that would be that bad. Even a global thermonuclear war would probably only kill 75-85% of humanity before the population started rising again (sorry Sagan).
Remember that every single one of your ancestors survived at least the Toba Catastrophe (only 10,000 human breeding pairs left on the planet) and probably many, many other events that seemed very-much like the end of world from their perspectives. All of them lasted at least long enough for you to eventually exist, and most did it without any knowledge of germs, plumbing, or literacy.
Civilizational entropy is my big wonk. I work under the premise that we're in the twilight of the West (read Oswald Sprengler) and problems that previous generations could have shrugged off will be far more lethal to us.
My focus tends to be on resource depletion, with secondary interest in climate change/natural disasters and war/tyranny.
Keep a supply of food on hand, grow reasonably hardy crops, know what kind of edibles grow in your local area. I don't believe in anthropogenic global warming, but I do believe in a gradual change by natural cycles of warming and cooling, as well as rapid change by e.g. sunspots. So I keep it in mind that agriculture in my area could look very different by the time I die.
I don't consider extraterrestrial life to be a pressing concern (though I am very annoyed by all the unelected scientists and bureaucrats who would presume to contact and negotiate with them on behalf of the entire planet). But if they exist and turn out to be not unlike most intelligent societies, that problem would be filed under tyranny.
The planet wouldn't be completely flooded. At worst, you might have something like entire oceans being thrown across continents by a polar shift or asteroid impact (apparently that actually happens in some new movie that I'll wait another decade before seeing). What would one do about that? Own a boat, or live near sealable mineshaft.
Lots of survivalists seem to have this mental image of refugees storming their homesteads like zombies or criminals using the breakdown as an opportunity for extra business. While that is a good reason to invest in some defenses, I think that for most people the future will look more like the past and present: boring.
During Katrina, we didn't see hordes of marauders bubbling out of New Orleans to pillage, rape and murder rural residents (violence did occur, but not as much as the early hype suggested; no rescue choppers shot at, for example), nor have we seen it in Detroit or any of the other odd-dozen major cities that are slowly rotting from the inside out.
Americans are too fat and pampered for any real organized violence. What most of them will probably do is mindlessly set around waiting for a rescue that's never going to come; people who've gone their entire lives without ever having to fight for their survival don't suddenly become more energetic when they have to, they become less.
That's why I consider being as self-sufficient as possible to be as important as stockpiling. Whether you have a week of supplies or ten years of it, unless you can get more you're living on a finite budget that'll eventually run out.
Incidentally, the idea of having a truckload of food and some seeds so you can bug out to the mountains and instantly become a subsistence farmer is foolhardy. My family has living in the same area for over 200 years and I've been gardening since I was old enough to walk and I'm still learning things. If I was going to start farming from scratch post-crash, I would want absolutely no less than two years worth of food to live off of before I actually started harvesting anything.
Mental preparation is probably the best kind you can do. That's one good reason to study the survival techniques of primitive/pre-industrial/pre-petroleum people who lived in your area.
If nothing else, live healthy and remove any addictions you might be on while you can still do so in comfortable conditions.