I've frequently noticed in anime seasons the title of a series or film will have an English letter at the end of the title (for example: Dragon Ball Z, Sailor Moon S)- what is the significance of the letter?
At least in the examples you've given, the letter helps differentiate a sequel show, or later season, from the original.
For example, the original Dragon Ball was followed by Dragon Ball Z, then Dragon Ball GT, then it gets complicated but they remade Z in a condensed form as Dragon Ball Z Kai and now there's Dragon Ball Super.
For Sailor Moon, the seasons after the first were Sailor Moon R, Sailor Moon S, Sailor Moon SuperS and Sailor Stars.
It's related to the practice of adding punctuation marks to a show's name to indicate later seasons, as discussed in this answer with examples like Working!! to Working'!! to Working!!!.