I think Lesli did a good job embodying Lois. I remember they (unwisely) reshot flashback scenes from Rena's run with her and Ned, and she pulled it off for the most part. But Lois as a character needed a very good reason to be back full time, and there wasn't one. They tried to clumsily slot her into the post-2000 mob-obsessed version of the show by pairing her with Lorenzo in C-story (as in, the only stuff not mob at that time) to keep him away from Tamara Braun and it didn't suit the character at all. So LK couldn't win for losing.
I don't think the role needs Rena to work, but I do think Lois (like Marty on OLTL) was a singular moment in time as a contract player unless you come up with something excellent or have very solid day to day writing. The corps GH had in place at that time was still fairly solid but the stories largely sucked, especially in 2003-2005. So neither Lois (nor Marty IMO, and Marty is one of my all time favorite characters) had a truly compelling reason to be back as a full time contract player.