That's one of those questions that is impossible to answer without hearing the tracks and the context. Obviously, the advice would be a lot different if you are talking about acoustic guitars in a bluegrass production, or heavily distorted guitars in a heavy metal piece. In general, you would go for different tones by using different guitars, different pickups, humbucker or single coil, neck or bridge, tube amp or solid state, or same guitar, same amp, different mics/positions. So many variables.
Maybe sharing an example would be helpful.