Additional Comments . . .
Given that you'll never achieve anywhere near 250 HP with this engine - why make the "big cubic inches" your goal? A well built flathead that makes 150 HP in a light coupe will perform beyond your expectations.
1) Bore: There is no reason to go beyond 3 5/16 bore. Save some block meat for a potential future rebuild. I never go to 3 3/8 for anything on the street - makes no sense.
2) Cubic Inches: A real nice combination is a 3 5/16 bore and 4 1/8 stroke - this is 284 cubic inches. With the right combination of parts, you'll find this to be a great street combination.
3) Cam: I'm not a big fan of either cam . . . for me, I'd run a Potvin 3/8 in that cubic inch range. Another popular cam is the L100 or Kiwi100.
4) Carbs: You'll probably find that for a stout street engine, that two carbs will probably run better and be easier to tune that three. I'd probably run an Edelbrock Slingshot manifold and two 97's or two 48's. You could even use a complete setup from Edelbrock (with their 94's) - they make good stuff and support their products well. You'll find that 97's are a bit easier to tune . . . but that is just personal preference.
5) Porting: It is one thing to polish the ports and clean up the bowls (street port), a very different thing to dramatically increase port size and flow. It is easy to "hit water" on the intakes if you're a newbie . . . as there are some real 'thin places' that you'd need to know about. I wouldn't recommend more than a street port for your setup anyway - unless you plan to spin the thing beyond 4500 rpm regularly (not many do that!). If you're not really experienced in porting in general, you may do more harm than good.
6) Ignition: Don't run a 49-53 stock distributor - is junk. There are plenty of options, you might want to chat with "Bubba" - he is one of the ignition gurus on this site. Me, I like magnetos - but that is just me. There are a lot of dual point Mallory setups that run well on 49-53 engines, converted SBC distributors . . . many options.
7) Transmissions: As many noted, the S-10 gear sets are almost useless. Also, having a .72 or .82 overdrive will result in a reasonable RPM drop in overdrive. Personally, I like the .82 - then I setup my final gear ratios and tire sizes to match.