Here's #41! Click here for the master list!
This was a fairly tough call, as two great writers began memorable runs on the 41st issues of their respective titles, but in the end, I think Alan Moore's debut on Supreme, due mostly to the fact that he was ALAN MOORE at the time, outweighs Garth Ennis' debut on Hellblazer, due to the fact that Ennis was just garth ennis at the time.
There was a great deal of hype surrounding one of the greatest comic book writers of all time taking over a Rob Liefeld character, a lot of "how could this be good? I know it WILL be good, but HOW?!?!" and Moore put all the fears to rest by turning the book into a love letter to the Superman stories of the 50s.
Moore did updated, but still optimistic (as opposed to cynical takes on the old stories, which seems to be what lots of writers love to do, as it is is a lot easier) takes on Superman and Superboy and all that jazz.
Meanwhile, he managed to work in a great deal of metafictive elements to the work.
Just a grand run on an awesome comic (I believe it even was later published by Awesome Comics ;) ). Chris Sprouse was very good on the artwork, too.
Ennis' run on Hellblazer is great, too.
Other memorable #41s....Rhino made his debut in Amazing Spider-Man #41, with a GREAT John Romita cover, FF #41 was a good Lee/Kirby issue and Tales of the New Teen Titans began with #41.