I've been careful with keeping my new PC nice and clean and purdy, particularly since this is my first PC I've gotten with a windowed panel (internals don't have to look their best when they're not being shown off). As far as that goes, let me just say that prevention goes a very long way. I try to keep my area clean and as dust-free as possible, so whatever gets sucked up is only the stuff floating around the air. My case comes with "dust filters," but as to not impede airflow, they are really nothing more fancy than the mesh screen you might see in a clothes dryer's lint screen. It stops some of the bigger stuff, but the fine particles still make it in. There was hardly any build-up in there, so I gingerly wiped it away with a microfiber cloth, as well as using a very slightly dampened lint-free cloth to pick up some extra stuff where surfaces allowed (like case surfaces, fans, cables, heatsink, plastic GPU cover). I also rinsed out all the filters until they were like new again. Using a handvacuum, I can clear most of the filters without even having to move the drive bay covers. Anyway, I've now added a ghetto mod, if you can call it that, where I've covered the whole front face of the case with some pantyhose. It's very quick and easy to do, the pantyhose has much denser fibers than the case's regular dust filters so that it catches more (but has no noticeable impact on airflow or temps), and it has the additional benefit of covering any gaps between the bay covers. It's easy to change/remove for cleaning or replacement, too.
I usually just use that handvac to clean out the other computers if they're super dusty. It has a little nozzle attachment for the end that focuses the suction in a much smaller area; it makes it easier to aim in tighter spaces and increases the suction power. Most of the stuff comes right up....just have to be careful not to hit and break anything. If you really need to get the rest of the finer stuff up, compressed air usually does the trick. I also like to use that in conjunction with the vacuum - blow from one end and suck the dust up from the other so it doesn't just settle elsewhere.