having done this several times...
I will tell you everything I look at. jadnashua hit most of the stuff already.
First thing is what kind of houses you are looking at. ranch homes on slabs can be tough and will require breaking concrete most times (something I don't do).
Most of the houses I have done are two story victorians with basements that allow good access underneath.
First floor powder rooms in a house such as this can be put almost anywhere, as the new plumbing can be run from underneath. You must watch out for where you are going to put you venting though.
As for second floor baths keep the following in mind:
1) you need supply lines- This is usually fairly simple to do given there small diameter and the flexibilty of PEX. Bath layout doesn't matter much because 1/2" lines can be put through floor joists without much effort.
2) you need drain lines- This will need to be 3"PVC. If you find a room in the second floor you'd like to make a bath, figure out how you will get 3"PVC down to the basement. Thick interior walls for this can sometimes be tough to find. You can be creative though and 'steal' an unused corner of the 1st floor room under the bath to 'box-in' the drain/waste line and the supplies. You also need to consider the layout of the Bath as getting the drain line from one area to another can be difficult with the floor joists. Keep in mind if the Flooring you see in a room is tongue and groove planks, the floor joists most likely run oposite of them.
3) You need vent lines- perhaps most often forgotten. If you are building new walls with the bath it is usually easy to run the vents up the new walls and into the attic then up through the roof. again pay attention to planned layout as it can help or hinder where you put all of this.
Finally- no matter what you see and plan for early on, add about 1/4 or so to the budget for the unforseen problems that WILL, not may, occur. If you end up with money left over, throw a big party and invite everyone that helped on the project and the forum members here too
if you don't plan on running into problems.... well just make sure to plan for them
Hopefully that helps some. If you have more questions let us know.
Oldhouse