As Game Master, you should think carefully about the type of campaign you woud like to run. Think carefully about which rules most closely simulate the events of your inspiration and choose them. At the same time, make sure you are familiar and comfortable with the rules you choose. Just as important as compatibility between style and rules is compatibility between GM and rules. Also bear in mind things like character creation and advancement.
Characters are naturally the focus of any good roleplaying campaign, whatever the genre.
You should chose rules whose character generation sequence creates the kinds of characters you want in your game. It's your game and, as GM, you should consider these factors in advance. Choosing the Setting Almost as important is the choice of setting. In some cases, the choice of rules will dictate that. The rules choice has great bearing on setting choice as well.