With the electorate pretty evenly divided between those self-identifying as Democrats, Independents, and Republicans, little changes in the rules tend to have a huge impact. The two biggest recent changes, which are probably pretty obscure to most Americans, are the Supreme Court's decision today allowing the key parts of the McCain-Feingold campaign finance reform law to stand, and the recent fights over redistricting.
Because Democrats have, in recent years, been much more dependent on unregulated soft money donations, the conventional wisdom has it that the new campaign finance rules banning such donations hurt Democrats more than they do the Republicans (though donations to interest groups are still unregulated, so the damage may not be as great as some are saying). Regardless, it certainly represents the next step the weakening of parties, who even now have very little in terms of mobilization capabilities.
The redistricting issue may prove to be a much bigger deal. In Texas and Colorado, the Republicans have violated the once-per-census norm of reapportioning congressional seats within states (that is, you only do it once every decade, after the census results come out). That, coupled with sophisticated computer systems that can pinpoint voting tendencies more or less down to the block, has let the Republicans pick up a significant number of seats in Texas (the Colorado plan has been stayed by the courts) - possibly enough to stave off a Democratic House of Representatives for some time to come. Jeff Toobin had a great article on this in the New Yorker last week.
Regardless of how it all shakes out, I think the Democrats are in a good bit of trouble. In many ways, it's their own fault for not being as well-organized as the Republicans and being unable (or unwilling) to fight the same sort of redistricting battles. And on the money side of things, whoever wins the nomination is going to go up against Bush, who has already proven his ability to raise tremendous amounts of McCain-Feingold-approved cash.