if your talking about big twins?
going up on trans sprocket is more efficient than dropping rear sprocket, I like 46 to 48 tooth rear gears, with 24 to 25 tooth tranny sprockets, & a FLH first gear in tranny, so I dont notice any power loss when taking off, & a light weight bike, depending on shape of engine, & cam, or other work, can still be good for interstate.
if your running early pan trans, you can even get a 26 tooth, front sprocket, but personally I like to stay with 24 on later shovels, & have no clearance issues.
you can even play with motor sprockets, just be careful that you dont gear too tall that you cant pull a hill. a fresh engine with some performance upgrades can pull alot taller gearing than a stock 74" can, & deliver better gas mileage as well, & as engine wears out, you will notice the loss of power on mountains or interstate when doubling first, & either drop gearing, or freshen engine.
if bike is totally stock, dont go lower than a 48 on rear, unless your quite a bit lighter, & even then if tranny is a 24, you may notice some power loss, if tranny is a 23, you will be fine. if a 24, & you need more power, think of a cam upgrade.
my last bike I had a 25 engine sprocket, 24 tranny sprocket, & a 51 & a 48 rear, I had 2 sets of rims, & was planning a 46 swap, I have used them in the past, as I was looking for better mileage. the engine was a 74" .030 over, cone shovel with high compression, ported heads with dual plugs, & performance cam, S&S E carb, & I normally got low to mid 50 MPG & best of 58mpg, with the 51 sprocket a best of low 50's & average close to 50mpg, my next bike I want to see if I can sneak into the mid 60's.