I recently purchased a 2008 Audi S5 and since day 2 it has been misfires non stop. At one point the car was basically a 4 cylinder. When I bought the car there were no engine lights, and no issues. We even managed to drive it 3 hours home with not a single issue.

Currently we have 3 misfire codes, P0300 (Random/multiple cylinder(s) - misfire detected), P0301 (Cylinder 1 - misfire detected), and P0305 (Cylinder 5 - misfire detected) both of which are in the front of the engine. We have replaced all spark plugs, swapped coils, and even had the entire intake manifold off (for a separate issue (had to replace intake runner control actuator)) where we found very little carbon buildup that isn't nearly bad enough to cause misfires. When we were taking the intake manifold off we found some crazy stuff. The idiots that were in there last had 7/10 of the screws hand tight, with the other 3 glued on to the intake to make it look like they were properly screwed in when in reality they were doing nothing. (we believe they replaced the heads and got the wrong one for the drivers side of the engine which caused one of the screws for the intake to not line up at all). They also re-drilled, re-threaded, and helicoiled all holes for the manifold. Anyways, we figured that with all these issues, and the manifold being improperly installed that's what caused our misfires. So after some modifications to the intake manifold and stripping the crap out of a bunch of bolts trying to re-install the manifold, we somehow managed to torque the manifold down and get it properly installed. Unfortunately the manifold was not the cause of the issues, and now that we have brand new plugs in there and coils we know work, it seems the problem would be the injectors. Which, of course, are located underneath the manifold and we fear that if we take the manifold off again we wont be able to get it back on because of how bad the threads are. Thanks Audi!

So here are my questions.
How are these cylinders related? Do they use any common parts, have any common points of failure that might cause both to misfire? What else could cause both these cylinders to misfire? What else should I check before hitting the nuclear button and replacing the injectors? Any information, ideas, theories, would be MUCH appreciated.
About the engine codes.
How does the engine determine that the cylinder is missing? Does the multiple misfire code mean that other cylinders besides 1 and 5 are missing randomly? what triggers the P0300 code? Once again, any information on how these codes work would be MUCH appreciated.