SMUG, the answer to your question requires much more detail re the purpose of your design problem - why are you increasing the displacement? - more performance etc? What is the spec/use of the existing engine?
I agree with your approach on wanting to investigate the design boundaries using CAE tools. For this type of investigation I would use a 1D engine performance simulation tool (Optimum Power, Gamma or Ricardo) to analyse the potential performance gains from changing geometry and valve timings/lifts etc. Having obtained an optimum design I would then check that it was mechanically feasible by using a tool such as 4stHEAD that is described on the Blair website (others would be GT-Vtrain, Valdyn etc).
Finally the mechanics of the crank could be analysed either separately or linked, depending on what CAE tools I had at my disposal.
I have used Optimum Power's Virtual Engines 1D software in the design arena before and have experienced reasonable success with it. The key to using any 1D software is to appreciate and realise their frailties.
Regarding the Cam Profile Design and Valvetrain Analysis tools out there, I have recently heard very good reports on the Blair software and saw the Presentation he gave at the motorsport Symposium in London back in November. However Gamma and Ricardo also have tools for this application.
In high performance engines I have seen significant gains from investigating the coupled effects of the torsional vibrations in the crank and cam and how this will affect the ensuing engine performance.
I could go on for ages, but the bottom line regarding CAE tools is your own specific design applications, resources and future plans.
All CAE tools are very expensive and can only really repay their investment if they are being constantly utilised. Some may even be the proverbial "hammer to crack an egg" so it is important to know exactly what they are all capable of doing, their strengths and weaknesses, although the latter 2 may only be apparent after you start using them in anger!
Most people tend to play safe so the perceived "bigger" CAE suppliers get bigger at the expense of those that may suit your purposes better. The plus is that most CAE tools have yearly licences, so you can chop and change if you are fortunate enough to have the time to do so.
I think I've gone on for long enough!