Have you ever wanted to throw out your Monster Manual and just start over with a whole slew of new monsters? As I write up creatures for Stellar Quest and my Madlands Campaign, I find that the thought races through my mind with greater frequency. Once I start gaming in the Madlands, this urge shall pass. However, it does spark within me the thought of "What If?"
In many ways, playing in a game with a whole new selection of monsters to encounter would probably be too much for some players. Some people just aren't comfortable with new things, and prefer the old stand-by encounters with orcs, skeletons and dragons rather than the more unusual hyrknoff, orthans and trylun. There's a familiarity and comfort that comes from using the tried and true creatures from our gaming past. Players share a common experience that helps create an underlying foundation upon which an individual encounter is built. Starting over with new monsters means that the carpet has been pulled out from under them; there are no preconceptions to draw upon. That potentially makes it more difficult for players to invest creatively into a new setting, and that could cause them to lose interest in the game before the game can develop its own inertia and move forward as a viable campaign.
However, it is entirely possible to run a game with all new monsters. For example, a few years back, I ran a planetary romance game on a world of my own creation (using Grim Tales, an excellent D20 variant system by Bad Axe Games). All of the creatures on the world of Samardan were brand new, creatures I'd created specifically for the setting. Truth be told, most of the encounters dealt with sentient races, so I avoided a lot of the "lack of foundation" issues by turning the game toward social conflict and exploration. Still, it was a lot of fun for me to watch a world unfold with new challenges and new creatures. It took me in a direction as a GM that I hadn't gone in quite a while, and the resulting game was very satisfying to me. It was hard to find players to join us, but those that did really got into the setting and the adventures we created.
If you are going to introduce an entirely new ecology for your next campaign world, with either limited or no connection to creatures from common D&D experiences, I would suggest that you build into it somewhat slowly, introducing only a few new elements with each adventure. I'd also suggest that your first adventure be rather NPC-heavy, because players already know how social interaction works with NPCs, and so it gives them a foundation upon which to build as you add these new elements. As a final suggestion, I'd mention that it helps a lot if you already have at least a small handful of creatures available when you begin to introduce this ecology so that you can add them to your world detail and such (as part of tavern names or local heraldry, that kind of thing), to allow for a greater sense of verisimilitude.
Should you undertake such a challenge? I would definitely say "Yes," if you feel up to it. I personally found the experience very rewarding. However, don't just jump in without considering the impact this will have on your game first. Hopefully this post has given you something to think about in those regards, even if you are just adding new monsters from that shiny new monster book you picked up last week to your well-established game world. Players sometimes don't handle change well, but when they do, the rewards are well worth the effort.
Hope This Helps,
Don't Jog My Elbow
1 hour ago