For me, the franchise is lucky in the sense that most of its performers are atleast solid and quite a few are excellent.
There are ofcourse, some weak links. The three that spring to mind are:
Denise Crosby: Just a very limited actress. She popped up in Lois and Clark and was just as bland. She does nothing for me on screen...she always FEELS like she is acting.
Jennifer Lien: I always scoff when I hear people mourning her departure in favour of Jeri Ryan. Jeri was simply a far better actress. If it wasn't for Lien's almost bizarre voice she would have faded into the background for me completely. I just cant engage with her at all.
Anthony Montgomery: Just...weak. He seemed like he was trying but I just dont blame them for limiting him. He is too green, to bland. Its like watching someone trying to learn how to act. Perfectly pleasant but meh.
+1 Couldn't have said it better. I thought Crosby had the right look, but she just couldn't act well enough. It was a good thing she left. It also provided an interesting opportunity for her reprisals that came later ("Yesterday's Enterprise" and the Romulan half-breed).
Lien was beautiful but flat in character personality. Granted the scripts weren't all that great for her, but she didn't make the best of them.
I was also not fond of Marina Sirtis. She started off TERRIBLE. She became reasonably good by the end of TNG though. Not fond of her movie work, though.
Gates McFadden also started off a bit rough, but she pulled through later in the 3rd season.
Scott Bakula really didn't know what his character was until late in the 2nd season. But by then it was too late. He really shined in the Mirror Universe episode.