I've worked on top level assemblies with over 100K parts - on ST2 32-bit with 4GB ram.
As long as you keep the on-screen data to a minimum ie. only display the parts you need to see, you shouldn't really have any problems.
For producing drawing views use view configurations to reduce the data displayed - I specifically use 'display visible parts only' to reduce the part count for a drawing view.
For example, set the assembly to a front view, then on the Select group click 'Visible Parts' the RMB and 'Show Only'
This will hide anyrthing that is completely hidden. Now save it as a View Configuration and name it 'Front Visible' or something like that. You can then use this when placing your view (or apply it to an existing view.)
When using simplified parts there is a trade-off as simplifying will increase part file size slightly - and this will increase file opening times.
Once loaded, however, view manipulation will be better.
Use as few operations as possible when simplifying, and remember that you can add as well as remove (a simple block placed over the model may be sufficient) - I've seen it done badly and files have increased in size quite significantly.
Just out of interest how big are the assemblies? - I wouldn't class anything less than 10,000 parts as big.
bc.
2.4GHz Core2 Quad, 4GB RAM,
Quadro FX4600.
Where would we be without sat-nav?