As stated above, way more variables then just 2/4 barrel.
The Motorcraft 2V (V=Venturi, often called barrel. But holley had a 3-barrel (secondaries were a giant oval) but was still metered by 4 venturi boosters) tends to be a lower performing carb that has been proven many times to run at really stupid angles. also tends to get better economy. If you can't flow the air, but can meter fuel into the air correctly, you will have a doggy but economical engine. Swap that with a generic Holley 2V that generally has default metering (metering is more then just jets) set to rich, you can get a 2V that will flow more air and a lot more fuel. Power will go up and economy will go down.
A properly sized and set up 4V with non-mechanical secondaries (Holly vacuum secondary, Q-jet, Motorcraft 4V, etc.) is typically known for better economy while still delivering better power then what a 2V can do. Driven gently on the primary side of the carburator you get higher velocity thus better atomization going into the intake. Of course the metering has to be setup correctly, float level, idle screw setting, throttle blade angle, jets, power valve, air bleeds, needle valves, etc. Get any of it wrong (too rich or too lean), economy AND power will both suffer. A 4V will flow more air under high loads and thus perform better in the power.
Some interesting trivia on carburator ratings. The flow ratings are not absolute. To have flow you need a pressure differential. A 4V carburator is rated at 1.5" of vacuum. But a 2V carburator is rated at 3" of vacuum. The greater the pressure differential the greater the airflow through the same orfice (carburator in this case). Holley specs are easy to find, if you look up the 750 CFM 4V mechanical secondary carb it has the exact same specs on throttle blade and venturi bore on both primary and secondary. Look at the 500 CFM 2V, it has the exact same specs as the 750, just half the carb. Double the 500 should be 1,000 CFM, not 750.
The difference is the testing. Put that 750 CFM 4V on the flow tester, crank up the fans until you are pulling 3" of vacuum and it will be flowing 1,000 CFM. Manifold vacuum is the lack of air to fill the cylinder on the intake stroke. 3" of vacuum is roughly 10% loss in potential power. I remember seeing a dyno sheet (that I really wish I could find again) that showed manifold pressure during a dyno run. from idle up through about half the RPM window it was flat. No measurable vacuum. At the top end of the chart it was actually showing a vacuum reading that ramped up with RPM. The carburator was limiting airflow. This was a very nice digital reading with lots of decimal points to it, not your hand held tune up gauge. But it showed restriction at higher RPMs. That is why you always see oversized carburators making better peak HP numbers. They sacrifice low speed control for a bigger peak number. This also comes back to that comment I made about a properly sized non-mechanical secondary 4V maintaining good velocity in the primaries. That is a big key to good drivability.
Were you expecting a nice simple answer? While at it we can go into EFI a little bit as well. Since the computer does the metering the warning about going too big hurting you is pretty much gone. You can have a lot more airflow potential and still maintain good control over fuel delivery. But you can go too big as well, but things get a little different. Mass airflow meteres measure the air flowing into the engine, almost. There is a little sampling hole about the size of a small fingernail that measures a little bit of the air flowing through the sensor, the rest bypasses around. But it is all carfully made and calibrated. The smaller the MAF bore, the more that actually flows through the sensor portion and the more accurate it measures. Huge barn doors of MAFs it gets difficult to tell how much air is flowing through the little sensor and how much is going next to it. Like standing in a large barn door on a breezy day, where you stand will change how much you feel the breeze while standing in front of a small window at the other end of the barn you can get a much better feel for the air flow, especially at low speeds. Thus the OEMs tend to be a little small on the MAF sizing. They want to get a decent velocity through the MAF to get a better sample. Racers don't care about low speed performance, they only care about top end numbers, thus the racer parts are bigger. In recent years the controls in the MAF have improved and the bores get larger as things are more tightly controlled, getting a decent reading through the barn door in a light breeze. Actually the full tilt race motors don't even run a MAF, they look at manifold pressure to determine how much air is entering the engine. No MAF restriction. Few dyno runs they can program the curves to match the airflow of the engine and they are off to the races. Ford had to give up on the manifold pressure route as it wasn't accurate enough to meet emissions requirements. Also the MAF tended to add about 1/2 MPG to the mustangs as it could better control fuel delivery during normal use. Easier to control the quality of the MAF over the quality of all the parts that went into the engine (casting variation, machine tolerance stack up, etc.)
Back to the original question. A properly setup 4-barrel carb can offer the best in economy and drivability while offering better performance when needed.
