And never put precision machines like a grinder or anything used to produce finished dimensions anywhere near a steam hammer or punch press. The vibration will kill you.
You would probably need a variety of lathes, from a 10" tool room up to a twenty something with a long bed. Big horizontal and vertical milling machines. Radial drill presses and big planers. Big hydraulic presses. A wheel lathe. A quartering machine. A flanging machine. Big horizontal and table grinders. A big vertical lathe.
Provide access to each machine with material handling provisions such as an overhead crane or forklifts. Allow plenty of room around each machine for big parts and staging.
A concrete floor heavy and reinforced enough to handle all the weight and vibration, topped by wood blocks on end. These are easier on the feet as well as parts that get dropped.
Need more? Now go out and raise cubic dollars to do all of this. When you have all of it in hand, then we can work on layout.

Let's consider one thing here.

Are you designing a shop to work professionally five days a week or more, like they do at Altoona, Cumberland, Roanoke, and Strasburg? Or are you accumulating a bunch of tools, equipment, etc. from the scrappers, donors, etc. for occasional use if and when you need them?

The above commenters are raising valid points, but at the same time you can let the perfect be the enemy of the good. "Inconveniences" (not to be confused with safety hazards) that would drive working professionals insane or homicidal after a week or two of daily abuse can easily be tolerated for a few hours a month, if the alternative is dragging stuff across town/the county to some other shop. I think we all have some funky compromise in our daily and professional lives such as "I can load the bike in the car only if I load it from this direction, turn it this way, then flip the wheel this way.... but it beats the pain of setting up and attaching the bike rack." Most short lines have similar idiosyncrasies somewhere on their systems--plug in the charger before you leave if you want that loco to start the next day, or whatever.

One railway shop with which I am personally acquainted looks like a huge, chaotic conglomeration of vintage machine tools, with a few newer versions (programmable milling machine, etc.) added in. If you look at the place, you'd wonder how anything gets done. But the reality is that I've personally never seen more than two machines in use at any one time. Meanwhile, not too far away, there's another restoration shop with lots of elbow room and terrific projects under way that seemingly can only dream of acquiring all the geegaws, doohickeys, and devices the first shop has accumulated over the decades, unless someone dumps a bunch of money at them.

Confused again about intent - shortlines didn't have backshops........most could make more common repairs during general tightening up and boiler patching type overhauls, but had no heavy overhaul capabilities. Many had their mainline partners help them out with those infrequent specialized repairs......which they were generally pleased to do at cost to keep the traffic moving through interchange with the shortlines.

EBT and Sierra........maybe Nevada Northern, although they were part and parcel of a large industrial behemoth so their capabilities might have been different. HABS / HAER probably documented some representative shortline maintenance facilities before they were all gone.

dave

Here are some pictures from the recently demolished MKT Bellmead shop outside of Waco, Texas. The shop building was divided into two halves by a row of columns; the engine stalls were on one side, and the machine shop on the other. The locomotives came in one end, and the overhead crane was used to lift them to an empty stall and back. Each tool station had a small crane to help with moving heavy parts. There was a compressor/switch room built into the engine side of the building; a boilerhouse outside completed the complex. I apoligize for the low resolution of the pictures:

http://good-times.webshots.com/album/562041636IiWkmx

The building was practically gutted at the time it was demolished; having been re-used for other purposes. An organization was trying to get the beam crane; I don't know if they were able to.

http://good-times.webshots.com/album/562040949OLcmJw