i used to have the same sort of problem when i first started welding. On high pressure tanks (argon, co2, helium, trimix, etc) the valve on the wheel only seat when all the way closed (the ball seat is seated on the bottom), or all the way open (the ball valve is seated on the top).

The other thing i've had problems with is having dust or junk in the fitting between the regulator and the bottle. Before you attach the regulator to the bottle, check the mating surfaces of the regulator and the inside of the bottle, and be sure there are no burrs or scratches on either one. Also, be sure to crack the bottle's valve for a second before you attach a regulator - this will blow out any dust or junk that may have settled in the neck of the bottle that can make it hard to seal, or ruin your regulator.

You shouldn't have to really crank down on the fitting to seal it. If you put too much torque on it, you will damage the regulator fitting, and then it doesn't matter how clean or nice it is, it will forever leak a little bit.