Oh, it'll probably run. Don't know how a DIS will work, though.
Recently had experience with a 302 ford motor that was an air
compressor. Hadda a compressor head on the left bank & those 4 plug
wires tied to ground & a one barrel on the top. Filled the resivoir
tank in about 15 seconds. Ran real smooth too.

This is deja vu all over again.  When the early-mid 70s energy crisis
came along,  some people tried disabling cylinders in search of some
marginal improvement in gas mileage.    That's about what they got,
too, considering that the rest of the car was still the size of a river
barge and showed similar concern for aerodynamics and had what we today
would consider primitive engine controls and a tragicomically lossy
driveline.

Later, Cadillac came out with an automated V8-6-4 scheme that earned a
reputation for balky driveability; I'd imagine that most were
eventually hardwired into permanent V8itude.

Chrysler, GM, and, I think, Honda have some more-sophisticated schemes
on the market or in the works  now.  If I'm not mistaken, at least some
of these schemes shuffle the cylinders that are in powered use so as to
even out the wear.

Note that Honda disables one side of a vee engine, as you propose to
do, but uses some pretty sophisticated additional technology (apart
from the sophistication of engine controls needed to give people the
driveability they want) in order to get away with that radical
approach.

See for instance
http://www.ai-online.com/issues/article_detail.asp?id=462
http://www.popularhotrodding.com/enginemasters/articles/hardcore/0405sc_gmdod/
http://www.popularmechanics.com/automotive/auto_technology/1266926.html?page=3&c=y

All in all:  yes, you can figure out how to do the mechanical aspects;
and yes, it will buy you a few to several percent in mileage; whether
it's really worthwhile is up to you (and whether your engine computer
will prove to be a show stopper, as mentioned by others, I dunno).

Cheers,
--Joe

Chrysler is currently doing this with their HEMI engine.  
------------
Alex

Caddilac's IMPLEMENTAION was a major failure. I haven't heard a single
gripe about the Chrysler MDS (Multi-Displacement System) as implemented
on the 5.7 Hemi in the 300C, Magnum, Charger, and Grand Cherokee (truck
Hemis don't currently get MDS).

But either way, that's a different ball of wax than permanently
disabling half the engine. With MDS, the whole engine is available for
quick warm-up and immediate power whenever needed.