For the # of layers you're looking at, there's no overriding reason to go with any of the large packages you mentioned.
For board size, you mentioned fairly small boards (up to 6x6), but then you said the future could be smaller or larger. You need to have an idea of what you need.
For the simulation, you repeated exactly what I typed (digital, analog, RF), but then said higher-frequency projects may be needed in the future... RF is kind of assumed to be anything from a few MHz on up into the GHz (THz?) range. The packages you mentioned don't simulate RF, per se, and there are specialized packages that handle RF much better than a package designed for schematic capture. Again, you need to have an idea of what you need.
As you said, since they are expensive packages you need to be sure what to buy... but you can't make that decision if you can't lock down what you need in such a package.
Altium (what I use) will set you back $5k for their perpetual license, though they now have year-long licenses that are <$1k. the latest version does a really good job of integrating CAD models into the design flow (I believe they are including a CAD modeler directly in the package these days, but exporting to IGES is a no-brainer for it).
Packages like MultiSim/Ultiboard are trying hard to get out of the hobby world, but they have a long way to go... because of that, you can find some really cheap packages in their lineup (and you get what you pay for).
I haven't priced Cadence in quite a few years, but last I checked it was already north of $10k/seat. Powerful, but way too much for anything I'll ever use as I'm not working on two foot square 20+ layer boards. As with all programs, Cadence also has (had?) a reputation for being quite quirky in its interface.
If you don't mind Linux, you should check out gEDA:
Surprisingly powerful package, open-source, and you can't get much better than free when you're tight on budget.
Dan - Owner