Space may not *require* notions of "up" and "down"...
... but Homo Sapiens certainly does.
This is basic cognitive science and psychology: humans evolved to walk on the crust of a planet. We haven't been brachiating for a very, very long time. This is bound to have an effect on how we design vehicles for any medium.
Aliens would likely have followed a different evolutionary path, so that will have a huge bearing on how they design their own travelling machines.
The TARDIS is a good example of the kind of lateral thinking you might see: why send the entire ship hurtling about the multiverse when you could achieve exactly the same results by keeping the ship tucked into a hidden dimension or 14, and move its cosmic user interface around the usual time-space frame of reference we're all familiar with instead?
Why SF has become so fixated on unfeasibly large boxes farting about through "hyperspace" (or some effectively synonymous equivalent) is beyond me. Doctor Who is actually quite refreshing in that sense. An alien is as likely to appear in a child's bedroom cupboard as in a giant spaceship with gigawatts of flashing, blinking, lights.