Since the SD Cards are slower than internal NAND memory, by running a ROM off the SD you will be sacrificing on the speed. Things like booting up and launching apps will be noticeably slower. The class rating of your SD Card will play a large role in how much slower your NC will feel when running in such configuration. It's generally recommended to buy at least a Class 6 card for this purpose.
By running custom ROMs from the SD Card you will be able to easily keep the original manufacturer installed firmware intact. In Nook Color the SD Card is set as a primary boot device, so if it contains a bootable ROM image, it will be used instead of whatever is installed on EMMC. By just inserting such a card into the microSD slot and turning the NC on, you will be running a custom ROM. Boot up without this card - and you're back on the EMMC ROM, be it stock or a different custom one. This can be quite beneficial for quickly testing out new experimental ROMs (e.g. Honeycomb builds) without blowing away your main one.
Although it's possible to multi-boot off EMMC without utilizing the SD Card at all, it's a lot more complicated to set up and maintain. This involves re-partitioning the internal memory, using a custom boot image, and modifying the start-up scripts for each ROM you'd like to have installed side-by-side. Needless to say, this type of installation is not for a novice.