I have always worked in environments with tight budgets, and little software budget.
If you have the money PSpice is an excellent tool and can handle almost anything you through at it. However, I have never had money, so I looked for free or low-cost solutions.
In my opinion the best free circuit simulator is LTspice by Linear Technology. Very simple to use, if you are even remotely familiar with PSpice, LTspice will be a breeze to pickup. The part library is obviously not as large as say Pspice however many common components are available. The simulator is lighting fast and very accurate, I've used to simulate power supply control loops and filter design and it does an excellent job.
Believe it or not Excel can be a very powerful design tool if you know how to harness it's capabilities. I found the Solver and Goal seek functions to be the most helpful , it can also perform Fourier Analysis which comes in handy. It takes a little getting use to but once you understand how to make it work for you, you'll wonder how you ever lived without. I've analyzed IIR filters using Excel and I've also drawn Root Locus Plots with it, very helpful.
I haven't tried any of the free MATLAB clones yet, however I plan on trying out Octave since I've heard good things.
Qucs is good, our RF guy wont use anything else.. plus its free, and theres kicad for circuit layout, now has 3D viewing of PCB, for maths calc, there is freemat...
If you can pay something then get Simetrix. It's excellent and written by a guy who is a good electronics engineer, not a software person, so it does what you want in a sensible way!
