I've always hit yes to this question in EOF before, but I know that if I hit yes for that too early it can screw stuff up if I'm trying to sync other tab in a song at a later point. My question is should I just always say no to this. Or say I've made a cdlc that just had a lead part and at a later point I add a bass tab, is there a way to remove that offset so I don't screw myself at a later point?

Generally, there is no need to reset offset to zero. Just keep in mind that the song starts several seconds (I think it's about 3 seconds) before the start of your beat map. In cases where you have a long intro before the start of the song, it's best to add some bars in the GP file you're using (if you are using) so that the beat map starts earlier and does not cut off the beginning.

I always add an empty measure at the beginning of the guitar pro file (with TuxGuitar) before importing it in EOF.

So, I don't need to add a leading silence in EOF (5 sec of silence only added on the soundtrack) nor to reset the offset to zero ...