But the µC itself runs on 3.3V and is not totally 5V-capable. You'd need level converters to interface with 5V.
> A separate, nominally 3.3 V, low noise supply (VREG_AVDD) is required for the regulator’s analogue control circuits.
It seems it would be painful trying to run this without 3.3 V.
The TL;DR is that 3.3v must be fed into IOVDD for 5.5v tolerance to work.
The chip needs a) 1.1V to power the cores, b) 1.8V-3.3V to power IO, and c) 3.3V to properly operate USB and ADC.
The chip has one onboard voltage regulator, which can operate from 2.7V-5.5V. Usually it'll be used to output 1.1V for the cores, but it can be used to output anything from 0.55V to 3.3V. The regulator requires a 3.3V reference input to operate properly.
So yeah, you could feed the regulator with 4-5V, but you're still going to need an external 5V->3.3V converter to make the chip actually operate...
Part of the GPIOs are CMOS are 5v-tolerant, and TTL considers 2v HIGH, thus it is possible to interface some 5v hardware directly.
I suppose the main draw of the regulator is that the DVDD rail will consume the most power. 1.1 V is also much more exotic than 3.3 V.