Yeah, cost is definitely an issue.
Other than the odd calibers (50 desert eagle, 454 Cassull, etc) does it make any sense for me to have a 45 and a 9 and a 40 and a 357?
The same goes for revolver. I've never shot a revolver. Does it make sense to have revolvers in similar calibers as well as the semi's?
I don't know. I'm in a gun-buying mood and am trying to maximize my dollar.
I would say that it does not make sense to have one of every caliber unless you just like collecting calibers. The reason is commonality of ammunition. If you have 10 different guns all of different calibers, then you are going to spend a lot of time hunting down all of the different varieties of ammo when going to the range, OR you are going to spend a lot of money keeping a decent store of ammo in all your different calibers. If, on the other hand, you have 3 9mm, 3 /45's, and 3 revolvers chambered in .38 special/.357, and 1 .22LR pistol for plinking, then you really only need to keep up with 9mm, .45, and .38 special (no one shoots .357 on a regular basis at the range and .22LR doesn't count due to the low cost and high availability).
Right now I have a 9mm, a .45, and a revolver in .38/.357. I was hesitant to pick up the revolver because I didn't want to keep a stock of another variety of ammo. To give you an idea, I have 600+ rounds of 9mm and 400+ of 45. I haven't built up a stock of .38 yet (only 100 rounds in the house). Why keep so much on hand? Well, I don't bother going to the range unless I plan to shoot at least 100 rounds through each of my pistols. If I bring a friend, we can really chew through some ammo and I don't want to hit the store looking for ammo before/after each range trip. I'd rather be able to depleat my stash over a few trips to the range, and then stock back up with periodic trips to a few select sporting goods stores (plus Wal-Mart). When the great ammo shortage of 2008/9 hit, it was painful and expensive for people to keep up with ammo supplies. People like me didn't worry too much.
Another reason not to buy something in every caliber is in case you decide to start reloading. I haven't made the investment in reloading equipment yet because of the time required to reload my own rounds is way too much for me right now. You've got to collect your brass, clean it, reshape it, then reload it. If you are really hardcore, you will buy materials to cast your own bullets! But, if I did get in to reloading, having only 3 calibers to reload would be nice. It would keep me from having to keep a bunch of different dies/equipment on hand, plus a bunch of different supplies for each caliber.
My future gun purchases will likely not stray outside of the 9mm, .45, .38/.357 or .22LR range. I would like to get a .22LR for super cheap plinking (plus target practice). My next purchase is going to be a small framed, lightweight pistol of some sort once I get my CHL. It will probably be a revolver, but I haven't fully decided. I would also like to get one of the evil black rifles (like an AR) for fun, but again, I don't really want to stock an additional caliber of ammo, especially .223/5.56 due to cost. So, I am looking into pistol caliber carbines such as the Beretta CX4 Storm (it would share magazines with my 92FS, another commonality advantage), or looking for an AR-platform "rifle" chambered in 9mm luger.
Anyway, I know this was a long post, but I wanted to give you a different, less is more perspective. And this was on pistols... don't get me started on shotguns!