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In theory, there are ways to get around things like the O2 sensor and the pumping loses. For example, you could block off your intake and/or exhaust ports on the deactivated cylinders, and drill holes through the deactivated pistons.
However, the issue that is going to be extremely hard (or even impossible) to get around is the vibration issue. This is going to depend a lot of the specific engine that you have. Engines that use cylinder deactivation have been specifically designed so that they're still mechanically balanced even when cylinders are deactivated. You have to realize that an engine doesn't really run at a "constant" speed--the crankshaft (and everything else) is constantly undergoing acceleration and deceleration. A lot is going to depend on the configuration of your specific engine (number of cylinders, firing order, cylinder V angle, flywheel design, etc.).
That being said, I'm not saying this can't be done--but you better really know what you're doing.
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