I think you first have to decide on a rough budget, and then decide how wild you are willing to put up with as a weekend driver.
For a relatively cheap, simple, reliable combo I would probably go with a high revving 327 or 350 (use good rotating parts & a strong cam) that runs in the 350 horsepower range, TH350 with a high stall converter, about 4.10 gears with posi, and the widest tires you can fit on the back. This combination should be relatively cheap (uses readily available parts), and give good performance in a '64 Nova. If built with good quality parts, this combo should also hold up to a lot of abuse.
You could also use a 4 speed, but the conversion from your Powerglide will require more parts and more time. A TH350 swap should be much easier. For real punch, you could add NOS, but I'm not really a fan of that idea.
There are many other SBC combos that would work (383 strokers, etc). and if you have a lot of patience you could run a BBC. However, most of them are more involved to build and will cost more money. How much pain (money) can you put up with?