Based on Cervelo's remarkable success with their P series bikes, most top-level time trial and triathlon frame design emphasize tight clearances so that wheels and other components can draft frame members, with the goal of presenting as continuous of an aspect possible into the airflow, so that its disruption is minimal. (You can click on the images below for more detailed views
Note the close proximity of the rear wheel to the seat tube in the photo above.
Not withstanding the success of this school of frame design on the road and triathlon circuits, there is a competing philosophy that attempts to factor in the impact that a forward rotating wheel has on overall aerodynamics.
As the thought goes, when a wheel rapidly spins forward, it also is creating forward rotation of air; when a wheel if fitted tightly to a frame, the frame's tight clearance creates a dam that blocks this secondary airflow, thereby creating unwanted drag. The company Look is a proponent of this philosophy. In the photo below, note the clearance between the rear wheel and the frame's seat tube:
In the 2012 Olympics, see how Great Britain's track bikes were designed with ample clearances around the crowns of their forks:
Recently, I've begun testing this design philosophy (greater wheel clearances mean less drag) on a Kestrel Talon, which has long proven to be a top aero performer in static wind tunnel tests. My goal is to establish how effective the Talon's rear wheel design is in comparison to the industry standard Cervelo P3C. So far, the preliminary results are interesting.