What level are you playing on?
Technology wise it's always good to go for Liberalism for the free technology (get Nationhood which is on the way to cavalry, Printing Press if you have lots of villages and Towns, or Astronomy if you need to go to another continent - or just the most expensive tech that is available). You need Philosophy for Liberalism and Paper and Education. Don't trade philosophy to anyone. Don't trade paper if you are still researching education, don't trade education either.
Good techs to go for after liberalism are Chemistry (for grenadiers, the AI loves rifles), Military Tradition for cavalry (if you get these before anyone else has rifles you can go an a rampage). Then you can trade away some techs to get what you missed out on while concentrating on liberalism.
Have you read Sisiutils guide for beginners in the War Academy? Lots of good info there re city specialisation.
Are you making sure that you have a steady stream of Great People so you can lightbulb techs? Great Scientists are normally best (apart from Engineers, they are much rarer though but there are ways to guarantee them).
If you already have grenadiers, cavalry and rifles by 1500 then other good techs to go for are Biology (more food from farms = more specialists), Physics (free Great Scientist if you get it first), Steam Power/Railroads (if you get machine guns first and put one in your attacking stack the AI hardly ever attacks you), Constitution is good if you run a lot of specialists because you get +3 research for each one).
It also depends what kind of victory you are going for. Concentrate on military tech if you are going for conquest or domination, science techs for space race (esp. computers for labs, robotics for space elevator), 1500 is too late to go for culture probably if you hadn't started out with that goal in mind, Mass Media for a diplomatic win (need lots of population so biology is important, and good relations with the AIs - except the AI with the most population which will be your rival).
Grab or trade for other techs as you need them. Need health? Get refridgeration for supermarkets or genetics later. Look ahead in the tech tree and see what effects each tech will have, if it sounds like something you are going to need soon then set that as your top priority goal.