Hrm, in my most recent full game (Noble/Standard/Medium&Small/Marathon), I was situated on a continent with Isabella and Augustus. Naturally, I had wars with the both of them... six with Augustus (I really only war to relieve cultural pressure on important cities... or if I'm attacked), and two with Isabella. Augustus kept up with me for the first two wars... but the last four were pretty lopsided, tech-wise. Macemen vs Praets for the third and fourth war... then grenadiers vs a mix of Praets/Macemen for the next two. Only reason I didn't finish him off sooner than I did is because... well, frankly, the peninsula I'd trapped him on wasn't exactly prime real estate.
I didn't wipe out Isabella in either of the two wars... but I did marginalize her to the point where she was a non-contender. The first war came a couple of turns after my second war with Rome. I took her capital and one other city... leaving her with 4 or 5 island cities. The second war only happened because one of her cities had pushed back my cultural borders... and stolen a Uranium resource, which was completely useless to her, considering the fact that she was using longbowmen/macemen at the time. I declared, sent a bunch of obsolete cannons/cavalry to that city, annihilated it, then sued for peace, mostly because I didn't want to go island hopping to wipe her out... and she wouldn't become my vassal.
In the closing turns of the game, I gifted her a BUNCH of techs, just for the hell of it. I swear it practically doubled her score.

Plus, I just felt bad about the two super-empires on the other continent picking on her. Albeit, I guess it's better that they picked on her and Kublai Khan, rather than messing with me... I may have been way ahead in military power during the Medieval, Renaissance and early Industrial periods, but I was middle-of-the-pack from the middle Industrial onward.