How would a hole in the side of a plane affect its flight?
Most planes fly best without any extra holes, of course! The specific effect of a hole is modifying local airflow, increasing turbulence, and increasing the aircraft's wetted area on the side of the breach. 

As long as there isn't a matching hole in the back, however, the airflow inside separates (similar to a pickup truck), so most of the airflow is still normal around the fuselage. The turbulence will also disturb flow over the wing root, if the hole is located forward of the wing, slightly reducing lift on that side. All in all, range will be reduced and more control inputs will be required.

Other than that, a hole in the side does not prevent a plane from operating normally. One can think of a conventional aircraft as the wing, pushed forward by the engine, and stabilized by the tail. The fuselage just connects them together and houses the payload (and controls, but we're not thinking about that at the moment).

Most fuselages are streamlined for minimum drag, but a plane can fly with a non-streamlined fuselage as well, just not as fast and not as far. Fixed-wing gunships, for instance, fly operationally with large holes in their side for the armament.