Which carburetor would be best for a 1956 F100 with a 292 Y-Block, with an Isky E4 cam on 110 degree lobe centers, mated to a T98 granny gear transmission? I am looking at a Holley 2300, 500 CFM two barrel performance carb, and a Holley 4160, 600 CFM four barrel street carb, vacuum secondaries. Which would be best for the aforementioned engine, cam, and transmission set-up? Or, would a different carb altogether be better? I have the intake manifolds for both types. Any advice will be appreciated.

You would be looking at better fuel economy with the four-barrel carb versus the 500 cfm two-barrel carb.  That’s simply a function of better fuel atomization due to the smaller size primaries.

As a general rule, always go for the larger cfm carbs with vacuum secondaries as the engine demand will dictate exactly how much the secondary side actually opens.  It’s hard to over carburate with a vacuum secondary carburetor due to the secondaries only opening up enough to support the demand of the engine.  I tend to use 750 vacuum secondary carbs on most Y’s that have an upgraded camshaft, better intake manifolds, and any kind of improvement performed to the cylinder head flow numbers.  For most near stock engines, the 600 vacuum secondary carbs prove to be more than adequate.

Just my opinion based on past experience so other comments always welcome.

Here are pics of the Summit and Steet Demon carbs which are proven performers on the Ford Y engines.
    

Lorena, Texas (South of Waco)

I'm running a 600 CFM Holley (1850) on my 292 now and it's fine.  I have been having issues recently that may be ignition related- it won't stop raining long enough for me to really test and tune...

Anyway, in my recent travels I stumbled on some insight that suggested that my carb was a bit on the large side.  When I got it, it had a 390 cfm on it, but that seemed way too small. The 600 wasn't the "night and day" difference I was hoping for...QuickFuel (a Holley Brand) makes a 450 CFM that would probably be a good compromise between the two.  

Thanks to all for the advice...4-barrel it is.