Just the obvious ones: a centerboard trunk is usually hard to service and it is hard to examine the pin and associated lifting gear to judge its condition. I love the idea of centerboards, but I would have concerns about accessing that mechanism unless I thought the design of it was inherently stronger than the rest of the boat. This is because in certain situations you don't want it stuck up or down, and if down, do you have the confidence that the lateral forces of rolling off a wave top can be borne by that pins and/or gear and/or cables, or that the trunk itself can remain intact should the keel come loose in the trunk, but not completely off.
Having said all that doom and gloom, I believe that if anyone has the larger cruiser/centerboard equation correct, it is likely to be Bristol. They make excellent boats. Little Harbors I know less about.
Killarney Sailor (Bruce) just bought a Bristol 45.5. He may have some comments on big centerboards.