I clean my PC about every couple of years, it's all about air flow as if you have conflict of flow you end up with pockets of 'trapped air' so to speak (stagnant air) therefore you have a build up of dust. Prior to getting 2000 rpm scythe fans, I still cleaned it every couple of years. I built it for my old bro's birthday before Ivy bridge was launched so it's fairly old.
The reason I got the 2000 rpm silent scythe fans (120mm x 120mm x 12mm) was to pull heat out of system given out by the XFX RX480 when over clocked. I also have a fan at the bottom of the case and the rear exhaust. They all are venting out, one of the scythe fans has been attached to the radiator and this fan (facing the motherboard) is venting out through the radiator and the other is attached on the top of the radiator also venting out (facing the top of the PC case).
This is the only place I could mount the radiator, prior to getting the GPU it was mounted on a side panel grill with the now bottom case fan venting out through the radiator. As I could only mount the radiator like this and as the metal side panels also helped disipate heat. The max stable overclock I achieved was 4.7 Ghz, but since it was not doing much it was reduced to 4 Ghz. (right now as the motherboard is dying it is on stock).
There is natural air flow into the PC through the other grills and other 120MM Fan grill (fanless).
In regards to dust, there is hardly any in the PC - I know that because I have had to clear the bios a few times and when installing my ssd I checked for dust and there was nothing. All the dust as expected was on the 2000 rpm scythes and some on the rear exhaust fan.
The other reason they have been mounted like this, they are directly above the GPU rear plate.
The PSU has been installed in way that the fan is facing upwards towards the motherboard and towards the GPU fans.
Previously when I had installed the fan, the "specialists" recommended it was to be installed facing down towards the floor against my instincts I did so just to see what happens. A few months later, all the components were caked in dust. I turned the PSU fan towards the motherboard and that reduced the dust build up a lot.
When I clean the fans and PC, it is off at the PSU but not unplugged to provide an earthing point. The fans are cleaned by holding the rubber blades and using a household vacuum cleaner (dyson DC39). You must hold the blades in position as you risk burning out the fans bearings. The radiator is cleaned with the vacuum cleaner and as everything else is pretty much dust free. It only takes about a couple of minutes.
TLDR:
Make sure the case has proper air flow and your lay out has zero chance for stagnant air to linger. Hold the fans in place using anything that does not damage them when using compressed air or a vacuum cleaner. If using a house hold vacuum cleaner (like a dyson vac) - vacuum from at least 15 cm in short bursts.
EDIT: NB: The PSU fan also vents out and does not blow air into the case.