There were a few replacements between the pilot and the main series. Dr Kyle was replaced by Dr Franklin and Lyta Alexander by Talia Winters (which coincidentally meant that the only two people who had actually seen a Vorlon were out). In addition, the XO Laurel Takashima was replaced by Susan Ivanova. These things required some rejiggering of various plot points and roles.How did replacing actors change the show? While needing to replace Michael O'Hare was a big deal, I'm not sure that any other replacements "changed the timeline" much, as it were.
There was Sinclair / Sheridan, Lyta / Talia (?) - the telepaths, G'Kar's assistant. Any others?
I think Takashima was originally supposed to have the Sleeper agent role that ended up being Talia Winters' job. And because Alexander was out, they couldn't explain the resident telepath gaining more power via Vorlon contact, and instead used the Ironheart plot from Mind War.