You have to tune to the leanest cylinder. You may have to live with that depending on your manifold and some other things like overlap and how well your headers work. You need to look at them all and make sure you know which plug came out of what hole and find the leanest one. And tune from there. And you have to check every plug, every time. When there is excess fuel blowing around in the intake any change you make may change the distribution characteristics.
If you have port EFI then you should be able to clean it up pretty good.
