You'll kill the motor in no time... one of the reasons it can't run on 4 cylinders for extended amounts of time is the heat problem...even though the engine is technically running on 4 cyls., the pistons and rotating assembly are still all cranking away...with no fuel being introduced into the cylinders, they still generate big amounts of heat...the motor will "cool" itself by running on 8 cyls more efficiently. Perhaps one of our tech savvy engine gurus can explain it better than I did? But I believe that to be the crux of the issue...not to mention that a powerful V8 under light load can cruise more efficiently than a 4 cyl under a heavier load at same speed...
Like was said, you'd likely use just as much fuel getting up to speed on 4 cyls as 8, if not more, due to the load...
About the only thing I think might be remotely possible would be for an electronics guy to somehow alter the "minimum throttle input" (for lack of a better term) settings to allow the motor to stay in 4 cyl mode for a little longer. What I mean is if you could cruise on the highway at slightly higher throttle inputs without it going into V8 mode? But let's be realistic, if it could be done to get significantly higher MPG, GM would have done this for us already...they know how strong a sales tool higher MPG is, so they would have tried to eke out every last bit of efficiency...but they also have to balance that against long term engine life...it would kill them if they achieved a 5% greater efficiency at the cost of engines blowing up in short order!
I guess bottom line is we all knew what kind of mileage to expect going in, and you just need to try to maximize efficiency by driving smartly...make sure your tires are properly inflated, you don't carry around any more weight than is necessary, you accelerate smoothly, you cruise at a constant speed in the sweet spot, trying for V4 mode as much as possible, etc...