My wife's family lives in DC, and they make it out here every year. The most important thing to remember is not to overdo things. If you aren't planning anything too difficult you should be fine. If you wait until you are thirsty, it is too late. Avoid alcohol and caffeine, get plenty of rest.
Oxygen deprivation can happen to anyone, even highly trained athletes who live at altitude.
Lots of flatlanders come out here and never have any problems with altitude. This year we don't. 4-wheelers while in the RMNP area. You can't use off-road vehicles in RMNP, but the Grand Lake area is surrounded with national forest areas that offer many offroading opportunities. There are several businesses in Grand Lake which rent ATVs, etc.