Wouldn't it depend on the gun more than anything?
If you're talking about something that can take a scout scope, obviously that won't interfere with iron sights. I've considered mounting a small reflex sight to a 10/22 on the forward half of the scope rail, as the rear attachment points for the rail are in use for a tech-sight, but there's no reason a small lightweight red-dot sight couldn't go on the other two screw-holes with a cut-down factory rail.
Of course with enough money and material you can do anything to anything, but if you want specific information you'll have to list a gun type or at least show a picture.