There is pretty much a rule against the Rogue 4 / Fighter 15 / Rogue 1 split.
As for what is allowed and what isn't, unless things have changed significantly since I was doing approvals, nothing is disallowed, although certain combinations (Monk / Druid is one, I believe) is looked at quite warily because of ease of abuse.
As with any single class submission, the background and character concept have to justify the multiclassing (i.e., why *must* he or she be a Fighter / Rogue instead of straight Fighter or straight Rogue?) and, as with any other complicating factor in a submission, requires more work from the submitter.
There is no rule, as far as I know, against multiple prestige classes, but they are extremely rare, given how difficult it is to obtain one prestige class and how much IC development would be necessary to qualify for and logically develop into two.