I am in communication w/ some developers on the Arduino Developers mailing list as I work on Arduino support for the SAM R21 E. I've figured out clock setup (so, hooray, Arduino setup actually runs!) ...however, USB CDC enumeration currently fails.
I had (erroneously) assumed the XTAL crystal could be 48MHz. In actuality (after reading the datasheet once more), it supports 0.4 to 32MHz, but can use the external crystal based clock source for DFLL (Digital Frequency locked loop) and FDFLL (Fractional DFLL) to generate 48MHz and 96MHz signals, respectively.
I had a look at the R21 Xplained Pro reference schematic, and it appears Atmel uses a 12MHz external crystal. I've ordered a couple of 12MHz crystals. I will retry USB tests once the parts arrive.