The 4.9 is hard to break, but gets crappy mileage, worse than the 5.0, and it doesn't have the power of the small block. The 5.0 is really more of a car engine, but is reliable, not many major issues I know of.
The 4.6 is also a good engine, but many guys say under powered. I think they are wrong. The 5.4 is also a good engine, but was never offered with a manual trans. Both the 4.6 an 5.4 had issues with exhaust manifolds warping and/or cracking. The 2V versions spit plugs, and the 3V versions are prone to cam phaser issues at high miles.
The 4R70 and 6R80 autos are both good trannies, as was the M5OD-R2. If you go manual I would stay away from the 97-04 Heritage body, the ones with torsion bar suspension. Getting the trans out without a lift is... difficult.