A fictional universe can be almost indistinguishable from the real world, except for the presence of the invented characters and events that characterize a work of fiction; at the other extreme, it can bear little or no resemblance to the real world, with invented fundamental principles of time and space.
The subject is most commonly addressed in reference to fictional universes that differ markedly from the real world, such as those that introduce entire fictional cities, countries, or even planets, or those that contradict commonly known facts about the world and its history, or those that feature fantasy or science fiction concepts such as magic or faster than light travel—and especially those in which the deliberate development of the setting is a substantial focus of the work.
Characters cannot be connected by characters "that do not originate with the publisher" — otherwise it could be argued that Superman and the Fantastic Four were in the same universe, as both met Hercules).
Specific fictionalized versions of real people — for instance, the version of Jerry Lewis from DC Comics' The Adventures of Jerry Lewis, who was distinct from the real Jerry Lewis in that he had a housekeeper with magical powers — can be used as connections; this also applies to specific versions of public-domain fictional characters, such as Marvel Comics' version of Hercules or DC Comics' version of Robin Hood.
Characters are only considered to have met if they appeared together in a story; therefore, characters who simply appeared on the same front cover are not necessarily in the same universe.