I had thought that the preposition “in” was used only with ablatives, but last night while reading chapter 10 of my beloved Latina Lingua,
I found said preposition in the company with a noun ending in -es. (3rd decl, plu, acc )… is there a difference between
in + abl and in + acc?
Salve gigas phoberos
“In” with the accusative signifies motion towards, so…
Cum accusativo, motum ad aliquod significat “in” praepositio, ergo…
He goes into the room in which he sleeps // > It/intrat in cubiculum in quo dormit
so in + abl indicates location inside, whereas in + acc is motion into something. (Seems obvious, don’t know why I didn’t see it). 
That’s it exactly. Adeò tenes.
In other places, the use of “in” with the accusative is a bit more mysterious. For example, in another post today I said “in antecessum” which means “[as payment] in advance”, where the motion is hidden, you might say! Or that’s one way of looking at it, anyway.
Ut alibi accusativo cum “in” utaris, minùs manifestum est. Exempli gratiâ, “in antecessum” nuper (hodiè verum dicere) scripsi, in quo motûs sensus abditus est, dicamus! Est una via, saltem, per quam rem imagineris.
Generally speaking, the accusative indicates motion towards something, while the ablative indicates a location, or movement away from something. This is a good basic rule to go by, though there are, of course, exceptions. This can also apply without prepositions, where the accusative will imply motion towards (cities, small islands, towns etc.), the ablative will imply motion away, and the locative serves for location.
I find that time also works well in this way. Ablative indicates the time at which something occurs, analogous to the location where something happens. Accusative indicates how long something takes, hence there is movement of time, analogous to the motion towards something.
There are two prepositions which can take ablative or accusative, in and sub. The differences in meaning with each case should be obvious.
sum sub mensa.
eo sub mensam.
“This can also apply without prepositions, where the accusative will imply motion towards (cities, small islands, towns etc.), the ablative will imply motion away, and the locative serves for location.”
Roma Brundisium it. Certainly pays to memorize those noun endings!
A&G gives the following (supplementary) information, also, which I think helps clarify the motion towards use (slightly modified/supplemented):
With the accusative, “into” (opposed to ex)
a. Of place: as in Italiam contendit, he hastens into Italy; as in casam currit, he rushes into his house.
b. Of time (till, until): as in lucem, until daylight; in noctem, until night.
c. Idiomatic usages from A&G which help clarify the sense of the accusative use: in meridiem, towards the south; amor in patrem, love for his father; in aram confugit, he fled to the altar (i.e., on the steps; merely to); in haec verba iurare, to swear to these words; oratio in Catilinam, a speech against Catilinam.
(In terms of my Wheelock’s experience (and so, presumably, Lingua Latina), the most important of these accusative uses are the place, time, and action against (i.e., in Catilinam, in Ciceronem) constructions.)
You could read that as suggesting “in urbe” means “away from the city” but you don’t mean that, ptolemyauletes, I know. You’re talking of the cases generally with, and then without, prepositions of all types.
Non vis dicere, ptolemyauletes, et “in urbe” et “ab/de/ex urbe” eundem sensum habere, certim scio. De casibus universè cum et absquè praepositionibus omnium generum scribis.