Okay, picking your brains ...
Assuming it is mainly clock-speed that is the complicating factor, how much faster than 16MHz could one safely run a microcontroller at, using simple double-sided PCB's, and a bit of care routing the PCB? After all, quite a lot of the high-speed stuff is internal to the microcontroller.
For example, an NXP LPC1343, which is a 32-bit ARM Cortex-M3.
It is lower-cost than an ATmega328+FTDI, has USB on-board, has about 36 I/O's, 32K Flash, but 8K RAM, about 13 PWM, 8 ADC inputs, and it's ADC is upto 25x faster than an ATmega328. It also has a built in bootloader that makes it look like a small USB flash drive (USB mass storage device), so upload can be done with the file finder, (or open, write, close).
If I just ran that on 12MHz crystal, internally at, say 24MHz, would it be likely that a stable double sided PCB could be made? Assuming, the peripherals, like SPI, etc are run at, say only a couple of MHz?
I'm interested in learning for a practical reason, not just theoretical 
GB-)