Tips on dealing with bulky/irregularly shaped pieces in drill press?

just shop it around to some automotive machine shops. If you only have the one manifold to drill, it might be easier/cheaper to pay someone else to hassle with it, ...or buy another manifold.
If you can't afford that, and are forced to drill it out, use a left hand drill bit, and run the drill motor in reverse rotation. When you relieve enough pressure on the threads, the bolt will just spin out. It can help to heat the threads up with a torch, and then quench it with penetrating oil. IMHO, the best penetrant is Mopar brand "heater control solvent & penetrating oil", but there are other good ones.