The only issues with 5.0 vs 289 are from the changes that Ford made when revising the 302 block to modern 5.0 specs. They made the crank pulley 4 bolt (same as 71-on 302), added a dipstick hole in the side of the block, changed the internal balancing to 50oz, revised the block slightly to fit a roller lifter camshaft, and deleted the hole in the side of the block that the Vintage clutch linkage goes into
Here's how to address these issues. The dipstick hole can be plugged with a 1/8 wooden dowel, a piece of cork, or tapped and fitted with a 1/8in NPT plug (from the hardware store). There are adapters sold by most Mustang places to use the old clutch linkage on a 5.0 ($50). There are conversion flywheels available from Summit for using an early model transmission on a 5.0 with the different imbalance. The 4-bolt pulley issue can be corrected by a 3 bolt conversion balacer (Ford Performance make the cheapest one), or you can steal the pulleys and brackets off a LTD or TownCar for serpintine, or steal the pulleys and brackets off of a 71+ 302 for v belt. Also, Ford Performance makes 4-bolt v-belt pulleys.
The quickest way, IMHO, to do the 5.0 swap (on an auto) is to use your front cover, accessories, brackets, waterpump, and pullies, and buy the Ford Perf. balancer. Plug the dipstick hole, and buy a TCI conversion flexplate from Summit. That conversion would be $75 for the balancer, and $60 for the flexplate. Good proceedure would be to get new motor mounts, waterpump, and fuelpump too. Your exhaust, intake & carb, ect will bolt on if need be. The 5.0 timing cover can be drilled for the original dipstick tube (not on 94+ or crate motors though), and you need to use an old oil pan.
As for EFI, MAF is easiest, and accepts modifcations painlessly, but often a little rarer. The myth that SD EFI cannot be modified is untrue; you just need to choose the camshaft carefully to avoid running/idle issues.
Personally, I'm building a carb'ed 5.0 with ported 351W heads, and I'm going to use big block chevy head bolt washers to compensate for the bolt size difference.
As far as EFI, the normal shocktower braces won't fit, and you either have to relocate the battery or use a shortened (Homemade) K&N setup to clear the stock battery, as M+ did with their EFI 289 GT Coupe. You have to provide for a return fuel line and wire it all up (which isn't too hard, just lengthy). To put in a return line, I'd just add a fitting to the stock sending unit. As far as the fuel pump, some people have had good luck with a frame-mounted F150 pump from a junkyard.
You can also use your stock waterpump with the 5.0 timing cover, contrary to popular belief (just ask JohnPro).
The squirrels in my head have spoken.
Cobra 5.0L & AOD swap, here we come.