I watched quite a bit of MLS this season. Only on TV as my 2 closest teams (Chicago Fire & Columbus Crew (Champions!!)) are both around 200 miles away.
Anyway the thing I most noticed is how much more time they have on the ball before getting closed down. If a player has only played in the MLS it would be a big adjustment to play in the top English leagues. I'm not saying they couldn't adjust but I think it would be a bit of a shock for them to suddenly not have 'half an hour' on the ball before getting tackled.
Seeing some of the games I reckon AFC Totton (currently top of the Southern League) would have half a chance of beating them!
If Saints could tie-in their academy with a USA one under some sort of agreement like 'Saints will take one player a year' then that might have some milage. England is a mystical, wonderful place in a lot of American kid's eyes - to have the chance to live there whilst playing soccer (yeah, yeah) would be a great incentive to them.
Saints could give them a year to prove that they can make it. If they fall flat then back to the USA they would come. Nothing ventured - nothing gained....
You'd need a good legal team to sort out the paperwork though. Otherwise Saints find them, train them for a year & then they p***ss off to some 'better' English club.
Of course if this were to happen it would be important for Saints to come over here and play some games. Somewhere central-ish - like Indiana.
Thinking about it - sod all this 'academy stuff' - Saints should just come over here and play. Bring a bunch of Replica Shirts to sell and the trip would almost be free.