The only mainline planes I have a problem distinguishing are the different series of 737s.

No problems with the A318/319/320/321... I look for the overwing exits for all of them (except the A318... and with that, I just know because it looks ridiculously out of proportion and stumpy).

The following is my personal guide to planes used in the US:

B737 - pointed nose; disproportionately tall tail; winglets (on some)
B747 - duh... the hump.
B757 - slender; rear part of engine nacelles; cockpit is "dropped" from main cabin level.
B767 - size; tail cone; "fatty" fuselage
B777 - rear tail "cone" (square, really); main landing gear (set of 3 on each side).
B787 - it's computer-generated.

A300 - it has "AA" on it
A320-series - those stupid wingtip things; bulgy nosecone.
A330 - big with 2 engines.
A340 - big with 4 engines.
A380 - big.

ERJ vs CRJ - different engine nacelles.

It also helps to know which airlines fly what aircraft. E.g., NW wouldn't be flying a 777.