Kevin,
You and I think along the same lines. For a street engine, I like longer strokes, more average hp/tq, and "sane" rpm levels. My street builds are generally hydraulic roller engines, about 10-10.5:1 compression, and usually peak at around 5500-6000 rpm.
With the FE stuff, all of the aftermarket crankshafts cost the same...no matter if it's a 3.98", 4.125", or 4.250". I always advise to go big.
Gas mileage is directly proportional to the weight of your right foot.
With a TKO 600, you will see your 12-13 mpg if you spend a lot of time cruising in overdrive. My favorite transmission/rearend combo for a Cobra falls somewhere in the 3.50-3.70 rearend ratio range, coupled with a TKO 600, .82 OD. You still get the lower cruising rpm (with 3.50, 55mph is at around 2100 rpm, 70mph is at around 2600 rpm) and the acceleration is that much more enjoyable.
I think you're putting too much of a wall between a 485hp engine and a 550hp engine. These days, there's not that much difference in part requirements. Generally it's just some head porting and a cam change. Unlike 30-40 years ago, 550hp is not considered a race engine, but I would venture to say that 500-550 is more of a "street standard". It doesn't take 12:1 compression, 7000 rpms, a huge cam, etc. It's done rather easily.
I get a lot of emails from customers wanting to do engine upgrades a year or so into the ownership of the car. They get used to the horsepower and want a little more. My advice is to get the most out of your money in the rpm range and parameters that you want to run in. Cams all cost the same price. Crankshafts all cost the same price. Personally, I'd like to get the best bang for my buck.
For your situation, I would do a 390 with a 4.250" crankshaft....445 cubic inches. Ported Edelbrock heads, ported Performer RPM intake, and a hydraulic roller. No maintenance, great reliability, 525-ish horsepower, gobs of torque.