Though this site has a very heavy war gaming and hobby focus, I still think t hat this is an issue I can address with some skill.
We've all been there, you have your story set, NPC dialog ready, enemy stats out, encounters planned. Only one problem, you are currently running your game with a slightly unfamiliar system. A player wants to do something, and you have no clue. What do you do?
Make something up. And stick to it. This is one of the most important skills you have to have as a GM. Your players look to you to provide a fun, fair experience. It's up to you how the game runs, but changing rules on the fly is not going to provide a good experience for your players. You need to stick to your guns.
Lets have an example. Your players are playing Dungeon Crawler, the Dungeon Crawling Game, where monsters are hit based on their DEF stat.
Ranger Tom is shooting at a skeleton, you, not knowing the the DEF stat of the skeleton, make up a number off the top of your head. Ranger Tom can't hit the skeleton because the DEF stat you made up for it is too high. Later on, Wizard Ian attacks a similar skeleton, and this time you have looked up the skeleton's DEF stat, and it is less high than the DEF you had given to it in Ranger Tom's encounter. But, you want to stay accurate to the rules, so you give it the lower DEF and allow Wizard Ian to hit and kill it. Now Ranger Tom is rather upset with you.
And you know why? Because you tried for accuracy over consistency. As the GM, it is your job to create a world for your players to experience, and changing up the rules in the middle of games will break immersion for your players, as well as giving certain players unfair advantages/disadvantages.
Of course, some of your players may not want you to do this. Generally, rules lawyers will want you to stick to the book as much as possible. What should your answer be? Ignore them. Your players need you more than you need them, your job is to make sure the majority of them have a good time. If you do something right, and consistently, it'll seem like you haven't done anything at all. As as the GM, that is exactly what you want your players to think.