What a loaded question.
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IMHO, I agree with most of the responses. Assumming you leave the truck stock, you'll see better fuel mileage with 3. 54's. I think the only time you'll actually see a 4. 10 out perform 3. 45s (on fuel mileage that is) is basically at max. tow rating (or maybe even exceeding max tow rating) and any towed weight above that. That's where the 4. 10s will have a fuel consumption advantage, among other advantages at that towed weight.
Definitely unloaded, your best mileage will be with 3. 54's. Anybody who thinks that you'll get better fuel mileage at 2,200 rpms at 65 mph, vs. 1,700 rpms at 65 mpg is just plain ole ..... well, I won't say it. Regardless of the fact that at 2,200 rpms the engine consumes fuel most efficiently, you'll still use MORE. Not only are you mechanically pulling more air/fuel through the engine, but as the revs go up the turbo makes more boost, even at steady state driving. So the added boost really puts the screw to the fuel mileage. That's my $0. 02 worth.
Those guys with the boost gauges know that even on level ground, the higher the rpm, the higher the boost will level off at. More boost, more fuel, more power. IMHO, lower rpms are more beneficial to a turbo-charged engine than a normally aspirated engine, for achieving better fuel economy, for the reasons as stated in the 1st 2 sentences of this paragraph.
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Y2K 2500 Cummins ETC/DEE, SLT+, 4X4, Quad, LB, Intense Blue Sport, 3. 54 anti-spin, rear aux. springs (camper special), sliding rear window, all options except cab clearance lights including agate leather, totally stock, + a mpg increaser goodie. Since everybody else listed their toys, I will too.
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