If you are roped into refereeing D&D 4e.

Combat takes longer. I can't stress this enough. Once you initiate combat you are committed for the next 1/2 hour or hour resolving it if fought to the finish. In a four hour session the most I seen somebody do was resolve three combat encounter between the same number of roleplaying encounters. This can be a big shock for somebody used to 1st edition AD&D or OD&D. I was used to it because of GURPS so it wasn't a big deal for me.

Wizards had opted for a specific style of presentation for 4e adventures. One that most of the 4e community has come to expect. If you use pre-made adventures they will seem constrained and linear compared other RPGs.

The good news is that the individual encounters are often well written, challenging and fun. Another benefit of 4e is that it lays out the math for you. So you can quickly come up with encounters of different power levels.

Remember you don't have to run 4e the way the Wizards presents it. If you have any experience with other RPGs with tactically detailed combat systems, whatever technique you had developed will work well with D&D 4e. How I managed GURPS worked fine with D&D 4e.

I typically run a sandbox campaign. And whether it is GURPS, Fantasy Hero, Swords & Wizardry or my original AD&D 1st, the setting is what it is and players encounter whatever was in the locale. What this means in practice is that around 5th to 6th level (or double GURPS starting points) most of the encounters are underscaled. Only when they go to truly dangerous areas or encounter experienced enemies will they find anything comparable to their current skill level. The effect the few D&D 4e game I ran is that most combat encounters are quickly resolved when the players reach mid heroic levels (5th to 6th).

Hopefully this illustrate that there is more than one way of running 4e than what is typically talked about. The only part of D&D 4e that is hard to work around is the how the power system makes everything seem like heroic high fantasy. But that is a minor issue. Again pretty any type of style or plot that you ran in AD&D 1st you should be able to do in D&D 4e.