Lets start with what a 2 and 4 bolt main is anyway. What holds your crankshaft in are main caps. These are what the crank bearings sit in and most engines have 5 caps. A 2 bolt cap is fastened to the block by 2 bolts and a 4 bolt cap has 4 bolts (2 on each side).
Main caps are the only thing keeping your crank from falling out the bottom of your engine. When you increase the load on the crank, you inherently increase the load on the main caps. Any time you increase horsepower, torque and cylinder pressure, you increase crankshaft load. It would take quite a bit more stress to rip-out 4 bolts than it would just 2, so that's why the 4 bolt mains are stronger than the 2 boilt mains. This is the theory behind it anyway. I have to say though... I have never seen a crank get "blown-out" of an engine, be it a 2 bolt or a 4 bolt main engine. I have seen engines "blow-up", leaving pieces of crank and engine block all over the track but it is usually due to metal fatigue and failure somewhere else and not the main caps blowing-off.
I have also seen 2 bolt main engines in low budget race cars running 9 and 10 second et's that last season after season. The more compression / cylinder pressure an engine has, the more the crank is trying to be pushed out the bottom of the engine, especially when a blower or nitrous is used. A way to make a 2 bolt main block even stronger than a 4 bolt block is to use a "main support". This is a brace that bolts across all 5 main caps, thus tying them all together and sort of creating a 10 bolt main engine. The theory behind this is simple, if one main cap tries to come-off, it has to take all of the others with it at the same time because they are all inherrently attached to that main support. It dispurses the load across all of the main caps evenly. One can't come out without taking the other 4 with it.
If you are going to be building a street engine that has 11:1 compression or less, then a 2 bolt main block would be just fine. Anything higher than 11:1 or so, or if you are going to run nitrous or a blower, then I would definitaly recommend a 4 bolt block, or a 2 bolt block with a main support just to be safe.
Think of it like this, ALL of the early Vette 327's with 365 and 375HP were 2 bolt main blocks. There was no such thing as a 4 bolt main 327. How about the infamous 68 "MO" 302 Z/28's which were famous for 8,000RPM shifts in stock trim! They came stock with 11.25:1 compression and were indeed high winders that saw race track use quite often, and they were also 2 boly main blocks!
How about the famous Shelby GT-350's? Well ALL of those were 2 bolt main "K code" 289's as well, which also saw 6,000-7,000RPM use VERY often. Now ask yourself, how many Vette's, early Z/28's or Shelby's have you ever seen on the side of the road with the cranks blown out? I'm not saying you should go out and build a race engine using a 2 bolt main block, but I want you to understand "reality". If you're building a sub 425-450HP engine, a 2 bolt main block will be just fine if it is set-up well, especially if it's a short stroke engine. Bigger stroker's are another story... if you are wanting a Chevy 383 stroker, I would suggest using a 4 bolt main block simply because of the longer stroke.
Now, the 351W Ford's on the other hand are only 2 bolt mains but I would ventire to say that they are stronger than a 4 bolt main Chevy. Why? Because the main caps and about 50% thicker than a Chevy, and the 2 bolts they have are huge 1/2" bolts, not little 7/16" bolts the Chevy's use. So as always, when dealing with subjects like this you have to compare apples to apples.