I leave the access panel off my machine specifically because it'll collect dust with or without it, and leaving it off means I blow out the inside more often (I guess that's sort of the computer equivalent of having a pickup truck forever parked in the yard with the hood up). By far, the two most dust-prone areas are the main fain and the card fan. Fans are a two-edged sword; they help keep things a little cooler but with diminishing returns - by pulling air they actually get choked themselves and get less and less effective.
Anyway, that's a roundabout way of suggesting you blow out the fans about once every 2-3 weeks. Use canned air and avoid breathing in the dust, if possible.
