Currently behind my 350 I have 2.25 inch piping on the head pipes and tail pipes. I plan to drop a 454 in there. Whether optimistically or not, I think I will be making enough power to want to run 3'' pipes, which is what I'll install anyway. My question is should I upgrade to 2.5'' on the tails or are the 2.25's ok? Does it really matter much after the muffler?

In a word, yes, it does.

If you've got 3" pipe back to the muffler, and then 2 1/2 inch for the tail pipes, you're just introducing the restriction further down in the system. As to how much of a difference this makes, I don't know, but I can't imagine it would cost all that much more to add in new tail pipes. If you're hard up for cash, just install some turn downs for how until you can afford to have full tail pipes put on.

I figure you could get away with 2 1/2" tailpipes, as the exhaust cooling has reduced it's volume. IMO, the 2 1/4" are way too small for a healthy big block though.

Here's a guy who tested the difference on his 462" Pontiac. It actually makes very little difference, about .03 seconds in a quarter mile.

http://www.pontiacstreetperformance.com/psp/exhaust.html

I run 2.5" tails, and I do think the answer is that the more the exhaust gas cools, the less pipe it needs. The only issue is sound quality, you're going to get one heckuva 'trumpeting' sound from such a small tail.