3d design tools and top down design are a good way to sort through the iterations and keep the number of accidental interference/mismatches down to a minimum.
My company uses Pro-E currently but we are part way through a shift to Catia so i have some experience using both products. I'm sure that most other 3d programs have the means to do top down design. As a comment, Pro-e is easier to create drawings and Catia is easier to create models. Both have a learning curve that is steep at the beginning.
One of the most important considerations at this point is, what is your design criteria. Who is your customer and what is important to them. My customer is my own company as we design out own machines. Our most important consideration is down-time, so we spend extra money when the decision between longevity vs cost, or make sacrifices in floor space when it makes for easier removal/installation of known wear items. If you don't know whats important to your customer when you start then you may make poor decisions in the design phase.
Our usual process is to have 1-4 mechanical design engineers working on a machine about the size of a house with several hundred uniquely designed parts several thousand purchased parts a large framework and a 8-12 month design cycle. The most effective way to do this is to start with a skeleton model that everyone gets a copy but only 1 person has control over. As design changes are made at the skeleton level everyone updates it. If you attach your design parameters to the skeleton, your parts update accordingly with each iteration.
Our machines can be broken down into "stations" so it is easy to break up the work and the skeleton model has the floorplan information, the axis's(how do you plural that?) of movement, and a basic sweep of the mechanisms. As we complete our individual bits of the machine it gets put into a model that includes the skeleton so all the indivdiual sections find their home on their own.
We create a schedule of I/O that gets handed to a group of electrical engineers and basically their work is done while the mechanical parts are being fabricated. When the parts are done being fabricated the electrical engineers have informed us of the various IO box's sensors ets, that are required for the control of the machine, we put those into the model and generate a final layout drawing that includes panel placement, cable ways and flexible cable paths. Our electrical engineers also handle basic pneumatic design but if it gets complex we farm that work out. We have completely eliminated hydraulic power from our machines as it is messy and electric cylinders can fit into almost every place that formerly would have require hydraulics.
Then an Electrical Engineer and I go and have fun putting together this giant jigsaw puzzle with whomever we contracted to do the work. We have a mechanical and electrical on-site for the last few weeks of assembly and then another couple weeks as you work through the constant minor and sometimes major issues that arise in a complex electical/mechanical assembly.
As a comment, This is virtually unchanged from the way things were done at this company before the advent of 3-d modeling, but instead of a couple design engineers, it used to be 2 engineers and 5-15 designers with an 18-24 month design cycle.
