Slow PC Performance

I have a person with a 1TB drive that is running our software.  We are told when the drive space reaches 80-85% capacity that this will cause performance issues not only with the software but the PC over-all as well.  What are some of the factors that could cause slow performance with this machine?  

Here are some of my idea's but maybe you can add a few more?
- Defrag
- FS bus speed to low.
- How many people are accessing this PC as well as how many application are installed on it?
- Bandwidth?

Any further suggestions would be appreciated greatly.  Right now they have about 125gbs of space left on this server and they say it's performing slowly.  I don't know what OS it's running but I'm sure it's a Windows Box.
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Try running the performance monitor on the server.

Start > Programs > Administrative Tools > Performance

Add some PhysicalDisk and Network Counters and see if any of them are running high.
This should give you a good rundown of performance monitor and how to interpret the results
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