4-bbls offer more scope for tunning on an I6 ifnyou can package it.
The vac sec 600 4180c is probably the worlds best carb, easy to calibrate, and a lot of fun with the high flow head. That's why the 5.0 and 5.8 HO Windsor and Lima 370/460 4-bbl truck engines used it for years from 82 to 96. The other sized Holleys, the 465 mec secondary 4-bbls are very good too. You can't go wrong with a big one. One 465 4-bbl carb can make 290 to 330 hp with ease.
The smaller 2-bbls are harder to tune, especially when the cam timing is wilder than the stock six cylinders 256 or aftermarket 260 degree cams. David Vizard always said timing is touchy with the Holley 2-bbl in 350 or 500 cfm form, and the Autolite suffers the same issues. Going to a 4-bbl gives you much more scope to keep the primaries small. The secondary circuit can always we tailored to suit, even with mechanical secondary carbs. There is so much scope with a good old Yanky 4-bbl.
Down here, our Crossflow guys are running similar carburation to a 5.0 factory HO set up, and if its wild, a 650 double pumper tunned to suit is fine with a stove hot 250. So a 465/470 or 600 is great with a Classic Inlinhes head even if its only got 3300 cc's to suck with!
Carburation works like this...a 200 or 250 can use as little as 3 barrels worth of 450 cfm and give 180 to 220 hp,
A 500 cfm 2-bbl Holley is really only a 354 cfm carb, but will give 235 to even 350 hp if your engine is a high winder, but it will have worse drivablity than a 465 four barrel so its pointless trying to work a 2-bbl to the raggard edges. A 350 cfm is only 247 cfm rated like a 4-bbl, and the 300 cfm Autolite is probably only 212 cfm rated as a 4-bbl, too small to avoid drivability problems, even though it may make great torque and good power if tuned right.