Nowadays commercial flights fly established routes that aren't always marked by a VOR, the various commercial planes follow internationally recognized airways of which are known the various fixes in absolute coordinates, to better organize traffic. To be able to follow those routes with a good precision the commercial planes follow the flight plan inserted in the FMC, or if the plane is an old one with no FMC, the captain inserts the coordinates of the various legs directly into the inertial platforms.

Some planes do use GPS instead of inertial platforms, but those are the oldest planes around, on which the lateral guidance was added in recent times as an upgrade. Planes like the 737-200 or the various 727 (to say two names) that used to fly only VOR to VOR.

And yes, every commercial flight flies IFR. The pilots receive clearance to take off and to follow a SID (Standard Instrumental Departure) that inserts the plane into an air route (you can liken it to the road you follow with your car from your home to enter an highway on a long travel), from which the plane exits when on destination to usually use a STAR (Standard Terminal Arrival Route) to line up with the runway the plane had been cleared to land on.

Sometimes the plane vectored to land by the tower, but that depends by traffic or other environmental situations not allowing to use the standard arrival procedures.