The potion is not forever
You need to drink some more after a certain amount of time. If it really did work forever we would have living dead wandering around still. Lisle is still unaware of this due to having only been a recent user. (Being only 71, she probably only drank it within the last 40 years or so.)
The potion is forever, but does not prevent injuries.
While the soul can operate the body forever, said body still needs to be maintained, and is still susceptible to traumatic injury. If the body undergoes clinical death, then it will eventually rot. Hence, how Helen and Madeleine end up. At the end of the film, their bodies have rotted to the point where they literally fall apart. If they had not suffered their fatal injuries, they would probably still be in one piece.
The small amount of the potion used on Ernest extended his lifespan
Since it rejuvenates his hand, it's probably that the effect eventually spread to the rest of his body. Since he was basically a broken down alcoholic
at this point, it's not likely that he would have lived all that long if he continued his life with Madeline. A small amount of the potion might simply slow the ageing process, as opposed to reversing it, since he has multiple children afterwards and a hugely active and much accomplished life after the age of fifty. It also explains how he got his aim back with his throwing arm and how he survived a plummet through the glass ceiling into the pool that should have killed him.
Helen's revenge plan wouldn't have happened had her therapist chosen her words better.
You see that as Helen's clinic therapist is giving her a harsh, but needed, talking to, Helen clings to her use of the word "eliminate" in accordance to Madeline. The therapist, of course, means she should keep Mad from her mind but Hel takes it as "inspiration" to decide to kill/take Madeline out.
If the therapist had instead chosen better words, maybe even gone with "the real revenge comes with living a better life without them" or something then Helen would have maybe just kept with the part of her plan where she taunts Helen with her success and good looks. Maybe steal Ernest back through non-lethal means or something- or found a better beau altogether. One whom Mad wouldn't be able to steal away.
This would have worked all the better since Mad most likely would have ended up dead anyway,her fight with Ernest would have still happened, would have still been bitter, and who knows. She might have fallen down those stairs anyway. And then Helen would have the youth, the beauty, the fame, the love interest - and Mad is a walking corpse.