I don't know if anyone will care, but I also use the biscuit joiner by Ryobi. I don't use it often, but is does a nice job with wider mouldings. However, lining up the holes is essential. I did some experimenting as to how to rectify the situation and came up with a method that works for me. I'm not saying that it will work for everyone or that it is perfect, just that it works for me.
First, I take the long and short pieces that are to be mitered together and lay them rabbet up, bottoms together on my workbench. I take the fence completely off the biscuit joiner so that it acts more as a thumbnailer. I then make sure that my mouldings are not going to slip. I line the biscuit joiner up on the 45 degree angle, let the RPM's build up and then make one cut across the two pieces of moulding. I fill the holes with glue and break the biscuit in half and pop it in. I let it set in the vise until the glue dries. Then I sand off any excess on the bottom. It's amazing how tight those little suckers hold! If your miters are true you shouldn't have any problems.
Unlike Ron, I am not a "tool-freak", but I did make his homemade jig. The jig works wonderfully and will no doubt make a nice compliment to biscuit joined frames!
I'm sure that some experienced woodworker is going to tell me how I'm defying physics or something, but so far its worked well for me!
Good Luck,
Tom