My first mill was a round column mill. Over the years, it has been used for a vast multitude of work ranging from large to very small. The largest was facing a 100 lb. anvil and the smallest had features that were less than .01" in size. I have a 12" RT on the table and have on occasion set it up for vertical operation so I could do four axis machining.
The 5.3" quill travel can be challenging but with a little planning ahead and creative choice of tooling, it isn't a problem for virtually all work. I use collets to hold drills so the tool offset is comparable to the end mills. A tap wrench and tap used with a tap follower in most cases comes close to the drill length. For larger drills, moving off the work to mount a tool is conveniently accomplished by virtue of the DRO..
In those instances where it is necessary to move the head, it is useful to realize that the y axis reference changes very little. I would set up a reference edge in the x direction and re-reference to that edge after the move. Where it isn't necessary to maintain .001" accuracy, a dowel pin mating with a hole before and after the move is sufficient. If I had a piece of work mounted in my vise with the vise jaws parallel to the x axis, I would loosen the work and mate the pin to the hole and reclamp.