Code P0300, HELP?

My 2000 bonneville SLE has recently thrown a P0300 misfire code. I have checked for Vaccuum leaks, and found none. Replaced the plugs with AC irridium, and AC wires. I put $20 of premium fuel and added Techron fuel system cleaner through it.
This started 2 nights ago driving home from work, when the check engine light came on and was running extremely rough. It would fall on its face when I accelerated and approached inclines. I was able to maintain highway speeds until I approached an incline. I had Autozone scan for codes the following morning and they found the P0300. I purchesed the plugs, and drove the car. The problem was much better, but still very noticable upon acceleration. Then I added the premium and the Techron. I did not notice any difference. The car will idle fine, but when I accelerate hard, it stumbles. The oil and coolant levels are fine. I do not want to keep throwing $ at this thing. Oh yeah, I also read that another individual had similar issues, and found the rear plug wire insulators were shorting. I had removed these also.
Any help resolving these issues will be greatly appreciated.

1) Try both a new air & fuel filters.
2) Check fuel pressure.
3) Clean MAF/IACT sensors.
4) Have your catalytic coverters back pressure tested.
** Plugged cats are known for random misfires.
5) Have both the battery & Alternator load tested.

I had a po300 code one time and the problem was the fuel pressure regulator. Do you smell gas under the hood?

I do not smell gas at all. I removed the injectors and fuel rail and did a good cleaning. I re-installed and tried the car again. Right away it started running rough at idle again. I did notice though, that when I heard the activation of the fuel pump, it started to smooth out. My next step is to check the fuel pressure. I have this bad habit of running almost out of gas before re-fuelling. I am sure this has not helped the life of my fuel pump. I have 153k on the car and the pump is the original. I do not have a pressure guage, so I will check with Auto zone on a loaner. I will keep informed.:dunno:

Very well could be a fuel pressure issue... I think iirc you need to be in the 50+ Psi range...

Check that pressure first... as well its not that hard to replace the fuel pump in the 00+ Bonneville... There is an access panel in the trunk for it...

Let us know what you find...

Well I stopped by a garage to have my convertor tested, and when I explained what was happening, he pulled out his diagnostic scanner and found 3906 misses on #5 and 3564 misses on #2. So I swapped out the coil packs, cleared the codes, and rechecked. The misses had followed the coil pack. So of to AutoZone and got a $25 coil pack to replace #2,#5 pack. Wallah, problem solved. Thanks to all you guys for your help. This site has helped me out tremendously.:ylsuper: