Well, you can go crazy and get the 80 pin QFP package, if you can work with SMD, or the 64pin PLCC package if you want, but that would be way overkill. The pins usually will not overlap functionality that you need. Even then, on the larger chips you still have to initialize each pin you are using with a variety of parameters, like whether you are using it for GPIO, or it's hardware block, like UART, I2C, SPI, whatever...whether it is currently being used for input, or output, .whether it will sink or source power...
I have a few 8pin chips, but I don't find them that useful, and I only bought them for their 'oh wow' factor. The only thing I ever made with them is a tiny IR transmitter. I usually buy the SMD 20 or 28 pin 4k/8k chips cuz they cover the functionality of the bulk of my projects and I don't have to stock a bunch of different chips. Also, with a discount for buying a bunch of them at once from Mouser, it works out well.
There's a limitation to the chips over 8k that they can only use resonators up to 10Mhz, otherwise you have to use a proper crystal timer. 8k chips and lower can use 20Mhz resonators. For something with important communication timing, you should probably use a crystal anyway.
Just because you know assembler on some other platform, doesn't mean you'll take to PIC or z8E assembler well. It'll be easier, but it's no given. I know 6502 and 80x86 assembler and had a very confusing time with PICs and their crazy paging schemes. z8E I know well enough now to make some basic functions, but that's about it. The hardware archetecture is harvard as well, not the oxford archetecture of your regular computer.
I'm thinking you should just get started with whatever uC you plan to use and then move on from there after you get comfortable with it. It's obvious from your questions, you really should get familiar with the uC first. I've never worked with the PIC 18series that has built in USB, Nigel might be right and you might want to try that. I was under the impression that it was fairly complex, though. Not as simple as the FT232.