There is one, possibly two sidequests in IV that are easy to miss if you are not really exploring the game but otherwise; beyond knowing enemy drops to get rare gear/enemy summons/and a token sidequest item, IV is relatively straightforward and doesn't need a guide.

V does, without a guide it is really easy to miss some of the summons, one of the Jobs, and getting some of the best gear. Not to mention the game introduces the Blue Mage class which is pretty smurfing broken if you know when and where to use them. You can beat V without a guide, but for one of the last game-centric entries until FFXII, I feel players owe it to themselves to run through with at least a Missable Guide once.

VI can also be beaten fairly easy without a guide, and if you're playing the GBA version, several of the game's tough choices are made moot. The only real reason to use a guide for this one, other than rare gear and a few of the espers, is that it does have a fair share of story sections that are easy to walk past or miss because you didn't realize it was there, or didn't bring the right party member along. Getting Gogo can also be tricky...