Make sure you are running with 'positive pressure', that is you have more fans intaking air than outputting air, this pushes air out of any gaps in the case and prevents dust getting in or being sucked in.
Keep the system off carpets and in a raised location, vacuum regularly.
To clean dust, you can use a normal vacuum cleaner carefully, compressed air or cotton buds etc. All while the system is off and unplugged though.
Clean House, regular dusting and filters = job done!
Positive pressure is as to what I tested one the easiest and best ways to keep dust out. The air pressure acts as the sealer of the case which prevents more crap/dust from entering. I did it and its a huge difference. Since I have a fan controller, I simply turned my main intake fan to higher speeds and my exhaust fans to lower speeds.
Note: Cooling will suffer a little bit due to this, but I believe positive air pressure is still better cooling than installing intake filters which choke airflow not just normally but even more so when they get dusty.
Once it gets a lot of dust, best way to clean is use a microfiber towel to wipe the basic surfaces and use compressed air to clean the components. I highly advise against using your own air compressor, use the cans they sell in stores. A regular compressor has air that can have moisture and be dirty. Air compressed cans are clean.