I'm actually a retired machinist and engine builder. I was hoping to avoid some research, just haven't done much small block R&D. Valve tip length is a consideration when using self aligning rockers, I am aware no other form of alignment can be in place. Just wondered if there were other considerations.
Drilling and tapping for an early manifold isn't difficult, my concerns were intersecting existing bolt holes and or water jackets. Ports are ports, I'll deal with that as necessary.
Now, as for the roller lifters and spider. Mounting the spider isn't an issue. Lifter bore depth, lifter length, oiling intersection, and will the alignment blocks interfere with the valley walls or are the lifter bores too short/long to work without modifications.
I'm looking for 450-500hp, certainly not out of reality.
On the issue of drilling Vortec heads for older conventional pattern...the end bolts do intersect the existing Vortec end bolt holes a bit, and the new bolt holes elsewhere on the intake face of the head are into very thing material, barely 1/4" thick so you don't get really good thread strength.
On the port location, Vortec port is about .120" higher roof that old school, so many old vintage intakes will have trouble making a good seal along the top of each port.
On the lifter deal, i believe it is the 3.4L V-6 lifter that gets you right for the early blocks...those earlier blocks have shorter lifter bores, that is why you cannot use later factory V-8 roller lifters, they are too tall.
You can drill the top of the center oil galley and using short spacers mount the factory spider. The lifter dogbones will require you to clearance grind the lifter valley wall and floor behind each pair of lifters for dogbone fit.
You've got an uphill battle shooting for 450+ Hp from 331 cubes w/Vortec heads....they are going to need some port work.
Factory hydraulic roller lifters are not going to like the rpm needed to get that much power....if you are familiar with machning, you can remove the lifter guts and make tubular spacers to limit plunger travel, making them work like the expensive aftermarket short travel high rpm roller hydraulics. Thin wall Chromoly tubing works well for this.
An alternative you may want to consider for endurance running is solid roller lifters on a hydraulic roller cam...popular with the marine endurance crowd, offshore boat racing.
The hydraulic cam profile lets the solid roller lifters live a ong life, you just have to tight lash them down around .005-.006" cold lash, in an effort to be as close to zero lash hot as possible without being too tight and holding the valve off the seat.